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

HRID 1485197Notes

Reaction equation

HRID 1485197 reaction equation
C=O.[NH:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH: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.C(Cl)Cl>[CH3:38][N:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:10]=[CH:11][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:13][CH:14]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601646962-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 712090912-(2-(2-(2-((4-(1-Methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Formaldehyde (37% in H2O; 15.6 μL, 0.210 mmol) was added to a suspension of 2-(2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (I1) (25 mg, 0.053 mmol) in anhydrous methanol (5 mL) under an atmosphere of nitrogen. Sodium triacetoxyborohydride (0.111 g, 0.525 mmol) was then added in one portion to the reaction mixture. The reaction was stirred at room temperature for 1.5 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (25 mL) and saturated aq. NaHCO3 (25 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) and dried over Na2SO4. The solvent was removed under reduced pressure yield a white solid. The solid was suspended in DCM (2 mL) and cyclohexane (10 mL) then filtered to afford the title compound (16) (19 mg, 73%) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 8.65 (s, 1H), 7.70-7.61 (m, 2H), 7.44 (s, 1H), 7.27-7.12 (m, 6H), 6.93 (s, 1H), 3.50 (s, 2H), 3.14-2.97 (m, 4H), 2.88 (d, J=10.6 Hz, 2H), 2.46-2.36 (m, 1H), 2.22 (s, 3H), 2.07-1.93 (m, 2H), 1.78-1.58 (m, 4H). LCMS Method C: rt 4.86 min; m/z 498 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (25 mL) and saturated aq. NaHCO3 (25 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  5. washthe combined organic layers were washed with water (25 mL), brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed under reduced pressure
  8. customyield a white solid
  9. filtrationcyclohexane (10 mL) then filtered

Sources & evidence

ORD record
ord-4834cfc4c17d40aa87623a983defa0fa
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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