Formaldehyde → HCID 73054313, compound

HRID 1779003Notes

Reaction equation

HRID 1779003 reaction equation
C=O.[CH3:3][C:4]1[CH:5]=[C:6]([NH:16][C:17]2[N:22]=[C:21]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH2:31][C:32]([NH2:34])=[O:33])[C:20]([C:35]([F:38])([F:37])[F:36])=[CH:19][N:18]=2)[CH:7]=[CH:8][C:9]=1[CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:3][C:4]1[CH:5]=[C:6]([NH:16][C:17]2[N:22]=[C:21]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH2:31][C:32]([NH2:34])=[O:33])[C:20]([C:35]([F:38])([F:36])[F:37])=[CH:19][N:18]=2)[CH:7]=[CH:8][C:9]=1[CH:10]1[CH2:15][CH2:14][N:13]([CH3:39])[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 73055445HCID 73055445, compound

Product 1

HCID 73054313HCID 73054313, compoundYield 89.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Formaldehyde (37 wt. % in H2O; 0.040 mL, 0.50 mmol) was added to a suspension of 2-(2-(2-(2-((3-methyl-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (11) (0.035 g, 0.070 mmol) in MeOH (5 mL) under an atmosphere of nitrogen. Sodium triacetoxyborohydride (0.19 g, 0.10 mmol) was added in one portion and the resulting mixture stirred at room temperature for 3 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL). Solid NaHCO3 was added until the formation of gas ceased then the layers were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with water (10 mL), brine (10 mL) and dried over Na2SO4. The volatiles were removed under reduced pressure to yield the title compound 12 as a white solid (0.032 g, 89%); 1H NMR (400 MHz, d4-MeOH) δ 8.52 (s, 1H), 7.53 (dd, J=8.4, 2.3 Hz, 1H), 7.44 (d J=2.2 Hz, 1H), 7.28-7.22 (m, 1H), 7.24-7.15 (m, 4H), 3.67 (s, 2H), 3.20-3.11 (m, 2H), 3.11-2.95 (m, 4H), 2.81-2.70 (m, 1H), 2.35 (s, 3H), 2.34 (s, 3H), 2.28-2.13 (m, 2H), 1.87-1.70 (m, 4H). LCMS-A: rt 4.908 min; m/z 512.3 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL)
  3. additionSolid NaHCO3 was added until the formation of gas
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  6. washThe combined organic layers were washed with water (10 mL), brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. customThe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-2c7cffe2531b4851beaa7bad0168f5a2
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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