Formaldehyde → 2-(5-Fluoro-2-(2-(2-((4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1778995Notes

Reaction equation

HRID 1778995 reaction equation
C=O.[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:14][CH2:15][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]4)=[CH:29][CH:28]=3)[N:17]=2)=[C:8]([CH2:10][C:11]([NH2:13])=[O:12])[CH:9]=1.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:14][CH2:15][C:16]2[C:21]([C:22]([F:24])([F:25])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]4)=[CH:29][CH:28]=3)[N:17]=2)=[C:8]([CH2:10][C:11]([NH2:13])=[O:12])[CH:9]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 730551532-(5-Fluoro-2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 730554442-(5-Fluoro-2-(2-(2-((4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Formaldehyde (37 wt. % in H2O; 29 μL, 0.39 mmol) was added to a suspension of 2-(5-fluoro-2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (9) (0.065 g, 0.13 mmol) in MeOH (8 mL) under an atmosphere of nitrogen. The resulting mixture was stirred for 10 minutes at room temperature then sodium triacetoxyborohydride (0.110 g, 0.518 mmol) was added in one portion and stirring continued for 3 hours The volatiles were removed in vacuo, then the residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (20 mL) and dried over Na2SO4. The volatiles were removed under reduced pressure to yield the title compound 10 as an off-white solid (58 mg, 87%); 1H NMR (400 MHz, d6-DMSO) δ 10.13 (s, 1H), 8.65 (s, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.49 (s, 1H), 7.22-7.16 (m, 3H), 7.08 (dd, J=10.2, 2.8 Hz, 1H), 7.04-6.95 (m, 2H), 3.50 (s, 2H), 3.12-3.04 (m, 2H), 3.04-2.95 (m, 2H), 2.87 (d, J=11.3 Hz, 2H), 2.46-2.36 (m, 1H), 2.20 (s, 3H), 2.02-1.92 (m, 2H), 1.76-1.58 (m, 4H). LCMS-A: rt 4.867 min; m/z 516 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued for 3 hours
  3. customThe volatiles were removed in vacuo
  4. customthe residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  7. washThe combined organic layers were washed with brine (20 mL)
  8. dry with materialdried over Na2SO4
  9. customThe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-19e053e4adfa4dbfaacbc4a28134e868
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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