Formaldehyde → 2-(2-(2-(2-((6-(1-Methylpiperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1779009Notes

Reaction equation

HRID 1779009 reaction equation
C=O.[NH:3]1[CH2:8][CH2:7][CH:6]([C:9]2[N:14]=[CH:13][C:12]([NH:15][C:16]3[N:21]=[C:20]([CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH2:30][C:31]([NH2:33])=[O:32])[C:19]([C:34]([F:37])([F:36])[F:35])=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:38][N:3]1[CH2:8][CH2:7][CH:6]([C:9]2[N:14]=[CH:13][C:12]([NH:15][C:16]3[N:21]=[C:20]([CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH2:30][C:31]([NH2:33])=[O:32])[C:19]([C:34]([F:35])([F:37])[F:36])=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 730543142-(2-(2-(2-((6-(Piperidin-4-yl)pyridin-3-yl)-amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 730546052-(2-(2-(2-((6-(1-Methylpiperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Formaldehyde (37 wt. % in H2O; 0.012 mL, 0.17 mmol) was added to a solution of 2-(2-(2-(2-((6-(piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (13) (27 mg, 0.056 mmol) in MeOH (2 mL) under an atmosphere of nitrogen. The resulting mixture was stirred for 15 minutes at room temperature before sodium triacetoxyborohydride (47 mg, 0.22 mmol) was added in one portion and stirring was continued at room temperature for 18 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL) then dried over Na2SO4. The solvent was removed under reduced pressure to give the title compound 14 as a white solid (25 mg, 90%); 1H NMR (400 MHz, d4-MeOH) δ 8.77 (d, J=2.4 Hz, 1H), 8.60 (s, 1H), 8.18 (dd, J=8.6, 2.6 Hz, 1H), 7.31 (d, J=8.6 Hz, 1H), 7.26 (d, J=6.3 Hz, 1H), 7.21-7.15 (m, 3H), 3.67 (s, 2H), 3.20-3.14 (m, 2H), 3.14-3.08 (m, 2H), 3.04 (d, J=11.7 Hz, 2H), 2.71 (tt, J=11.9, 3.9 Hz, 1H), 2.35 (s, 3H), 2.21 (td, J=12.0, 2.5 Hz, 2H), 1.96 (d, J=11.0 Hz, 2H), 1.92-1.80 (m, 2H). LCMS-A: rt 4.635 min; m/z 499 [M+H]+.

Workup

  1. additionwas added in one portion
  2. customThe volatiles were removed in vacuo
  3. customthe residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  6. washThe combined organic layers were washed with water (25 mL), brine (25 mL)
  7. dry with materialthen dried over Na2SO4
  8. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-59a5879c5b0f49dfad90065b45d1c5cc
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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