Formaldehyde → HCID 73055152, compound

HRID 1778989Notes

Reaction equation

HRID 1778989 reaction equation
C=O.[F: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>[F: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[CH2:11][CH2:12][N:13]([CH3:39])[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 73055150HCID 73055150, compound

Product 1

HCID 73055152HCID 73055152, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Formaldehyde (37 wt. % in H2O; 0.041 mL, 0.50 mmol) was added to a suspension of 2-(2-(2-(2-((3-fluoro-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (7) (0.046 g, 0.092 mmol) in anhydrous MeOH (5 mL) under an atmosphere of nitrogen. Sodium triacetoxyborohydride (0.19 g, 0.10 mmol) was then 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 organic layers were combined, washed with water (10 mL), brine (10 mL) and dried over Na2SO4. The volatiles were removed under reduced pressure to yield the title compound 8 as a white solid (0.043 g, 92%); 1H NMR (400 MHz, d4-MeOH) δ 8.58 (s, 1H), 7.66 (dd, J=13.2, 2.0 Hz, 1H), 7.37 (dd, J=8.5, 2.0 Hz, 1H), 7.28-7.14 (m, 5H), 3.68 (s, 2H), 3.20-3.12 (m, 2H), 3.13-3.04 (m, 2H), 3.01 (d, J=12.0 Hz, 2H), 2.90-2.76 (m, 1H), 2.34 (s, 3H), 2.24-2.12 (m, 2H), 1.90-1.77 (m, 4H). LCMS-A rt 4.888 min; m/z 516.3 [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. washwashed 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-50f128b357ca4b50adbe2876d80d6484
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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