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

HRID 1473149Notes

Reaction equation

HRID 1473149 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[C:29]([CH2:30][C:31]([NH2:33])=[O:32])=[CH:28][CH:27]=[CH:26][N:25]=4)[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:14]=[CH:13][C:12]([NH:15][C:16]3[N:21]=[C:20]([CH2:22][CH2:23][C:24]4[C:29]([CH2:30][C:31]([NH2:33])=[O:32])=[CH:28][CH:27]=[CH:26][N:25]=4)[C:19]([C:34]([F:37])([F:35])[F:36])=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601648082-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

Product 1

HCID 601648092-(2-(2-(2-((4-(1-Methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamideYield 72.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Formaldehyde (37 wt % in H2O; 16.5 μL, 0.222 mmol) was added to a suspension of 2-(2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide (32) (22 mg, 0.044 mmol) in anhydrous methanol (5 mL) under an atmosphere of nitrogen. Sodium triacetoxyborohydride (94.0 mg, 0.444 mmol) was then added in one portion and the reaction was stirred at room temperature for 2 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (25 mL) and sat. 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 to yield a white solid. The solid was suspended in DCM (5 mL) and cyclohexane (20 mL) and filtered to afford the title compound (33) (16 mg, 72%) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.06 (s, 1H), 8.64 (s, 1H), 8.36 (dd, J=4.8, 1.7 Hz, 1H), 7.59 (dd, J=7.7, 1.2 Hz, 3H), 7.53 (s, 1H), 7.20-7.13 (m, 3H), 7.00 (s, 1H), 3.53 (s, 2H), 3.24 (s, 4H), 2.91 (d, J=10.6 Hz, 2H), 2.47-2.39 (m, 1H), 2.24 (s, 3H), 2.12-1.99 (m, 2H), 1.78-1.59 (m, 4H). LCMS Method C: rt 1.51, 1.579 min; m/z 499 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (25 mL) and sat. 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. customto yield a white solid
  9. filtrationcyclohexane (20 mL) and filtered

Sources & evidence

ORD record
ord-2bf078082bd5469982f74cea1592113b
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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