106429-59-8 Archives - Imidazoles-derivatives

September 6,2021 News Share a compound : 106429-59-8

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, other downstream synthetic routes, hurry up and to see.

Synthetic Route of 106429-59-8, The chemical industry reduces the impact on the environment during synthesis 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, I believe this compound will play a more active role in future production and life.

To the solution of the crude product from Step 6 in MeOH (2 mL) was added NaOAc (14 mg), and 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde (21 mg). The resulting mixture was stirred at RT for 15 min, at which point NaCNBH3 (15 mg) was added to the solution. The resulting mixture was heated at 50 oC overnight to give a clear solution, which was purified directly by preparative RP-HPLC method E to give 5- fluoro-N-isopropyl-N-methyl-2-(1-(1-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5- yl)methyl)piperidin-3-yl)-2-thioxo-1,2-dihydro-3H-imidazo[4,5-c]pyridin-3- yl)benzamide as a TFA salt (1.20 mg); LCMS method B: Rt = 0.54 min; (M+H)+ = 574.6; 1H NMR (MeOH-d4): delta 9.01 (br, 1 H), 8.51 (s, 1 H), 8.21 (s, 1 H), 7.74 (s, 1 H), 7.38- 7.04 (m, 5 H), 4.65 (m, 1 H), 4.48 (m, 1 H), 4.31 (m, 2 H), 3.83 (m, 4 H), 2.87 (m, 2 H), 2.52 (m, 1 H), 2.15 (m, 3 H), 1.99 (m, 1 H), 1.32-0.82 (m, 6 H).

Reference:
Patent; VITAE PHARMACEUTICALS, INC.; CACATIAN, Salvacion; CLAREMON, David A.; DONG, Chengguo; FAN, Yi; JIA, Lanqi; LOTESTA, Stephen D.; SINGH, Suresh B.; VENKATRAMAN, Shankar; YUAN, Jing; ZHENG, Yajun; ZHUANG, Linghang; (285 pag.)WO2018/53267; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Extended knowledge of C8H6N2O2

According to the analysis of related databases, 106429-59-8, the application of this compound in the production field has become more and more popular.

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde

Step 5.5-((7-(5-((5-fluoro-2′-(1-hydroxypropan-2-yl)-[1,1′-biphenyl]-2-yl)oxy) pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (1143) (1144) To a suspension of 2-(2′-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5-yl)oxy)- 5′-fluoro-[1,1′-biphenyl]- 2-yl)propan-1-ol (20 mg, 0.45 mmol) and 2-oxo-2,3-dihydro- 1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 7.3 mg,0.045 mmol) in anhydrous MeOH (3 mL) was added NaBH3CN (5.8 mg, 0.09 mmol) under a nitrogen atmosphere and the mixture was stirred at 60-65 C for 16 h. An additional batch of 2- oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde (10 mg, 0.062 mmol) and NaBH3CN (7 mg, 0.11 mmol) were added, the reaction mixture was stirred at 60-65 C for an additional 18 h. The reaction mixture was concentrated under reduced pressure and purified by RP-HPLC-method A to give 5-((7-(5-((5-fluoro-2′-(1-hydroxypropan-2-yl)- [1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H- benzo[d]imidazol-2(3H)-one (TFA salt) as a white solid.Yield: 13 mg. LCMS method E: Rt = 1.752 min, (M+H)+ = 595.2 1H NMR (CD3OD): delta 8.45 (s, 1H), 7.74 (s, 1H), 7.07- 7.44 (m, 10 H), 4.35-4.50 (m, 2H), 3.40-3.95 (m, 9H), 3.10-3.25 (m, 1H), 2.75-2.85 (m, 1H), 1.95-2.20 (m, 4H), 1.00-1.25 (m, 3H).19F NMR (C MeOD): delta -117.47, -76.69 ~ – 77.90.

According to the analysis of related databases, 106429-59-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VITAE PHARMACEUTICALS, INC.; CACATIAN, Salvacion; CLAREMON, David, A.; DILLARD, Lawrence, Wayne; DONG, Chengguo; FAN, Yi; JIA, Lanqi; LOTESTA, Stephen, D.; MARCUS, Andrew; MORALES-RAMOS, Angel; SINGH, Suresh, B.; VENKATRAMAN, Shankar; YUAN, Jing; ZHENG, Yajun; ZHUANG, Linghang; PARENT, Stephan, D.; HOUSTON, Travis, L.; (444 pag.)WO2017/214367; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

The important role of 106429-59-8

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, its application will become more common.

Related Products of 106429-59-8,Some common heterocyclic compound, 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, molecular formula is C8H6N2O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a stirred mixture of intermediate 62 (120 mg, 0.32 mmol), 2-oxo-2,3-dihydro-1Hbenzo[d]imidazole-S-carbaldehyde (CAS: 106429-59-8) (104 mg, 0.64 mmol) and TiG-PrO)s (92 mg, 0.32 mmol) in DCE/DMSO(6 mL/2 mL) at 0 C was added NaBH(OAc); (205 mg, 0.97 mmol) in portions. The reaction mixture was stirred at room temperature overnight. The reaction was quenched with aq. NaHCOsand the resultant was extracted with DCM. The combined organic extracts were washed with brine, dried over anhydrous Na2SQOuq,filtered and concentrated. The residue was purified by prep-HPLC (Waters 2767/Qda, Column: Waters Xbridge 19*150 mm 10 um, Mobile Phase A: H,O (0.1% TFA), B: ACN) to give Compound 117 (22 mg TFA salt, yield: 13%) as a white solid.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; JOHNSON & JOHNSON (CHINA) INVESTMENT LTD.; DAI, Xuedong; QUEROLLE, Olivier Alexis Georges; KROSKY, Daniel Jason; CAI, Wei; FU, Liqiang; KONG, Linglong; LIU, Yingtao; WAN, Zhao-Kui; HERKERT, Barbara; PANDE, Vineet; EDWARDS, James Patrick; PATRICK, Aaron Nathaniel; ANGIBAUD, Patrick Rene; PONCELET, Virginie Sophie; (488 pag.)WO2019/120209; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Introduction of a new synthetic route about 106429-59-8

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde

Step 3. N-(2-amino-2-oxoethyl)-N-(5-fluoro-2-((4-(7-((2-oxo-2,3-dihydro-1H- benzo[d]imidazol-5-yl)methyl)-2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5- yl)oxy)phenyl)isobutyramide (1176) To a solution of N-(2-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5-yl)oxy)-5- fluorophenyl)-N-(2-amino-2-oxoethyl)isobutyramide (40 mg, crude) and 2-oxo-2,3- dihydro-1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 29 mg, 0.18 mmol) in anhydrous MeOH (4 mL) was added 4A-molecular sieves (50 mg), then the reaction was stirred at 50 C for 2 h under N2. After 2 h, NaBH3CN (28 mg, 0.45 mmol) was added into the solution and the reaction mixture was stirred at 50 C for 12 h. The reaction mixture was then filtered, concentrated under reduced pressure, and purified by RP- HPLC method G to afford N-(2-amino-2-oxoethyl)-N-(5-fluoro-2-((4-(7-((2-oxo-2,3- dihydro-1H-benzo[d]imidazol-5-yl)methyl)-2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5- yl)oxy)phenyl)isobutyramide as a white solid.Yield: 7.00 mg. LCMS method E: Rt = 1.498 min, (M+H)+ = 603.3.1H NMR (CD3OD): delta 8.30 (s, 1 H), 7.76 (d, J = 2.4 Hz, 1 H), 7.52 (d, J = 8.8 Hz, 1 H), 7.15 (t, J = 8.0 Hz, 1 H), 6.87-7.03 (m, 4 H), 4.73 (dd, J = 16.4, 3.6 Hz, 1 H), 3.82 (dd, J =16.0, 4.8 Hz, 1 H), 3.56-3.85 (m, 5 H), 2.45-2.69 (m, 5 H), 1.81-1.94 (m, 5 H), 1.05 (dd, J = 36.8, 6.8 Hz, 6 H).19F NMR (CD3OD): delta -119.24.

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

Simple exploration of 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

Reference of 106429-59-8,Some common heterocyclic compound, 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, molecular formula is C8H6N2O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Step 3.5-((7-(5-(4-fluoro-2-(3-hydroxypentan-3-yl)phenoxy)pyrimidin-4-yl)-2,7- diazaspiro[4.4]nonan-2-yl)methyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (0942) To a solution of crude 3-(2-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5- yl)oxy)-5-fluorophenyl)pentan-3-ol from above and 2-oxo-2,3-dihydro-1H- benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 20 mg, 0.12 mmol) in MeOH (3 mL) was added NaBH3CN (10 mg, 0.16 mmol) at RT and the reaction mixture stirred for 4 h. Evaporation of the solvent followed by RP-HPLC method A afforded 5-((7-(5-(4- fluoro-2-(3-hydroxypentan-3-yl)phenoxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2- yl)methyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one. LCMS method G: Rt = 3.197 min; (M+H)+ = 547.61.1H NMR (CD3OD): delta 8.52 (bs, 1H), 7.60 (m, 1H), 7.45 (dd, J = 2.8, 10.6 Hz, 1H), 7.21-7.18 (m, 2H), 7.11 (d, J = 8.4 Hz, 2H), 7.05-6.96 (m, 1H), 4.43 (s, 2H), 4.20-3.90 (m, 4H), 3.70-3.50 (m, 2H), 3.48-3.33 (m, 2H), 2.34-1.90 (m, 6H), 1.89- 1.80 (m, 2H), 0.78 (t, J = 7.2 Hz, 6H).

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

Application of C8H6N2O2

According to the analysis of related databases, 106429-59-8, the application of this compound in the production field has become more and more popular.

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 106429-59-8 as follows. Application In Synthesis of 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde

A solution of intermediate 2 (100 mg, crude HCI salt, 0.29 mmol) and 2-oxo-2,3-dihydro-1H-benzo[d]jimidazole-5-carbaldehyde (CAS: 106429-59-8) (71 mg, 0.44 mmol) in MeOH (2 mL) was stirred at room temperature for 2 h. NaBH3CN (37 mg, 0.58 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mixture was diluted with H2O and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na,SOu, filtered and concentrated. The residue was purified by prep-HPLC (Waters 2767/Qda, Column: Waters Xbridge 19*150 mm 10 um, Mobile Phase A: H20 (0.1% TFA), B: ACN)to give the racemic Compound 14 (49 mg, TFA salt). The obtained racemic Compound 14 was separated by SFC (SFC80, Waters, IC 2.5*25 cm, 10 um, A: Supercritical COQ., B: MeOH/DEA= 100/0.03; A:B = 70/30; Flow rate: 70 mL/min; column temperature (T): 25 C; Backpressure (BPR): 100 bar) to give Compound 108 (12 mg as TFA salt, 6.8% yield) as a white solid and Compound 109 (13 mg as TFA salt, 7.3% yield) as a white solid.

According to the analysis of related databases, 106429-59-8, the application of this compound in the production field has become more and more popular.

Research on new synthetic routes about 106429-59-8

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

Application of 106429-59-8, These common heterocyclic compound, 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Step 5: 5-((7-(5-(4-fluoro-2-(3-fluoro-3-methylbutyl)phenoxy)pyrimidin-4-yl)-2,7- diazaspiro[4.4]nonan-2-yl)methyl)-1H-benzo[d]200midazole-2(3H)-one and 5-((7-(5-(4- fluoro-2-(3-hydroxy-3-methylbutyl)phenoxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2- yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (0953) To a solution of 2-(5-(4-fluoro-2-(3-fluoro-3-methylbutyl)phenoxy)pyrimidin-4- yl)-2,7-diazaspiro[4.4]nonane (50 mg, 0.12 mmmol) in anhydrous MeOH (2 mL) was added 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 22 mg, 0.14 mmol) and NaBH3CN (23 mg, 0.37 mmol) and the solution was stirred at 50 C for 16 h. LCMS showed the desired compound and that the 2-(5-(4-fluoro-2-(3-fluoro-3- methylbutyl)phenoxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonane was consumed. The mixture was purified by basic preparative RP-HPLC method D to give 5-((7-(5-(4-fluoro- 2-(3-fluoro-3-methylbutyl)phenoxy) pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2- yl)methyl)-1H-benzo[d]imidazol-2(3H)-one and 5-((7-(5-(4-fluoro-2-(3-hydroxy-3- methylbutyl)phenoxy) pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H- benzo[d]imidazol-2(3H)-one, both products as a white solid. (0954) Example 35. LCMS method E: Rt = 0.618 min; (M+H)+ = 610.3.1H NMR (CD3OD): delta 8.23 (d, J = 5.6 Hz, 1H), 7.55 (s, 1H), 7.05-7.12 (m, 1H), 7.03 (s, 1H), 6.95- 7.01 (m, 2H), 6.85-6.95 (m, 1H), 6.70-6.75 (m, 1H), 3.63-3.83 (m, 4H), 3.61 (s, 2H), 2.72-2.78 (m, 2H), 2.60-2.70 (m, 2H), 2.48-2.59 (m, 2H), 1.78-1.98 (m, 6H), 1.33 (d, J = 21.6 Hz, 6H).19F NMR (CD3OD): delta -120.97, -140.72. (0955) Example 36. LCMS method C: Rt = 0.586 min; (M+H)+ = 547.3.1H NMR (CD3OD): delta 8.23 (s, 1H), 7.56 (s, 1H), 7.09 (dd, J = 9.22.8 Hz, 1H), 7.05 (s, 1H), 6.95- 7.00 (m, 2H), 6.85-6.95 (m, 1H), 6.72 (dd, J = 8.84.8 Hz, 1H), 3.69-3.83 (m, 4H), 3.65 (s, 2H), 2.49-2.75 (m, 6H), 1.90-2.00 (m, 2H), 1.84 (t, J = 6.8 Hz, 2H), 1.67-1.76 (m, 2H), 1.20 (s, 6H).19F NMR (MeOD): delta -121.18.

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

The important role of 106429-59-8

The chemical industry reduces the impact on the environment during synthesis 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde. I believe this compound will play a more active role in future production and life.

Application of 106429-59-8, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows.

Step 4.5-((7-(5-((5-fluoro-2′-isopropyl-[1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)-2,7- diazaspiro[4.4] nonan-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (0987) A mixture of 2-(5-((5-fluoro-2′-isopropyl-[1,1′-biphenyl]-2-yl)oxy)pyrimidin-4- yl)-2,7-diazaspiro [4.4]nonane (6.8 g, 15.7 mmol), 2-oxo-2,3-dihydro-1H- benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 3.05 g, 18.8 mmol), NaBH3CN (3.9 g, 62.8 mmol) and HOAc (3.4 mL) in MeOH (130 mL) was stirred at 70 C for 18 h. The mixture was then concentrated under reduced pressure and the residue adjusted to pH = 8 with saturated NaHCO3 solution and extracted with ethyl acetate (3 ¡Á 150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by basic preparative RP- HPLC method D to give 5-((7-(5-((5-fluoro-2′-isopropyl-[1,1′-biphenyl]-2- yl)oxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H-benzo[d]imidazol- 2(3H)-one as a slight yellow solid. Yield: 7.2 g. LCMS method C: Rt = 0.663 min; (M+H)+ = 579.1.1H NMR (CD3OD): delta 8.13 (s, 1H), 7.58 (d, J = 6.8 Hz, 1H), 6.95-7.35 (m, 10H), 3.62 (s, 2H), 3.40-3.55 (m, 3H), 2.55-2.85 (m, 4H), 2.30-2.45 (m, 2H), 1.65- 1.85 (m, 4H), 1.00-1.10 (m, 6H).

Some tips on 106429-59-8

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, and friends who are interested can also refer to it.

Related Products of 106429-59-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 106429-59-8 name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Step 4.5-((7-(5-((5-fluoro-2′-(1-hydroxyethyl)-[1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)- 2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (1074) To a solution of 1-(2′-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5-yl)oxy)-5′- fluoro-[1,1′-biphenyl]-2-yl)ethanol (330 mg, 0.66 mmol, crude) and 2-oxo-2,3-dihydro- 1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 106 mg, 0.66 mmol,) in MeOH (10 mL, anhydrous) was added AcOH (0.2 mL). The mixture was stirred at 17-25 C for about 30 min, then NaBH3CN (82 mg, 1.32 mmol) was added and the resulting mixture was stirred at 17-25 C for about 16 h. The mixture was quenched by sat. aq. NaHCO3 (10 mL) and extracted with CH2Cl2 (3 ¡Á 20 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to give a residuewhich was purified by RP-HPLC method A to give 5-((7-(5-((5-fluoro-2′-(1- hydroxyethyl)-[1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2- yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (TFA salt) as a white solid. Yield: 290 mg. LCMS method C: Rt = 0.593 min, (M+H)+ = 581.21H NMR (CD3OD): delta 8.00-8.15 (m, 1 H), 7.50-7.70 (m, 2 H), 6.90-7.40 (m, 9 H), 4.67 (s, 1 H), 4.43 (s, 2 H), 3.35-3.95 (m, 8 H), 1.90-2.25 (m, 4 H), 1.20-1.35 (m, 3 H).19F NMR (CD3OD): delta -76.92, -117.29 ~ – 118.17.

Brief introduction of 106429-59-8

Step 3.5-((7-(5-(4-fluoro-2-(2-methoxybutan-2-yl)phenoxy)pyrimidin-4-yl)-2,7- diazaspiro[4.4]nonan-2-yl)methyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (0935) To a solution of crude 2-(2-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5- yl)oxy)-5-fluorophenyl)butan-2-ol and 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5- carbaldehyde (Intermediate 40, 7 mg, 0.04 mmol) in MeOH (3 mL) was added NaBH3CN (8 mg, 0.13 mmol) at RT and the reaction mixture was stirred for 15 h. Evaporation of the solvent followed by purification by RP-HPLC method A afforded 5-((7-(5-(4-fluoro-2- (2-methoxybutan-2-yl)phenoxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)- 1,3-dihydro-2H-benzo[d]imidazol-2-one TFA salt. LCMS method G: Rt = 4.01 min; (M+H)+ = 547.62.1H NMR (CD3OD): delta 8.52 (bs, 1H), 7.65 (m, 1H), 7.34 (d, J = 9.6 Hz, 1H), 7.21-7.18 (m, 2H), 7.13-7.10 (m, 3H), 4.43 (s, 2H), 4.20-3.95 (m, 4H), 3.70-3.50 (m, 2H), 3.47-3.36 (m, 2H), 3.15 (s, 3H), 2.34-2.05 (m, 4H), 1.96-1.87 (m, 2H), 1.58 (s, 3H), 0.76 (t, J = 7.6 Hz, 3H).