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

HRID 1473041Notes

Reaction equation

HRID 1473041 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH2:28][C:29]([NH2:31])=[O:30])[C:17]([C:32]([F:35])([F:34])[F:33])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:2]1.C=O.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:38][N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH2:28][C:29]([NH2:31])=[O:30])[C:17]([C:32]([F:35])([F:33])[F:34])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:2]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601645862-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 601645872-(2-(2-(2-((4-(1-Methylpiperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 93.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 2-(2-(2-(2-((4-(piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (4) (0.021 g, 0.043 mmol) in anhydrous methanol (2 mL) were added a 37% aq. solution of formaldehyde (0.006 g, 0.195 mmol) followed by sodium triacetoxyborohydride (0.046 g, 0.217 mmol) under an atmosphere of nitrogen. The reaction was stirred at room temperature for 1 hour, the volatiles were removed in vacuo and the residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (15 mL), the combined organic layers were washed with water (10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (5) (20 mg, 93% yield) as a an off-white solid; 1H NMR (400 MHz, d4-MeOD) δ 8.54 (s, 1H), 7.62 (d, J=8.5 Hz, 2H), 7.30-7.15 (m, 6H), 3.67 (s, 2H), 3.19-3.12 (m, 2H), 3.12-3.02 (m, 2H), 2.96 (d, J=11.1 Hz, 2H), 2.85-2.74 (m, 1H), 2.34 (s, 3H), 2.13-2.03 (m, 2H), 1.96-1.67 (m, 3H), 1.49 (ddd, J=24.8, 12.5, 3.9 Hz, 1H). LCMS Method C: rt 4.86 min; m/z 498.3 [M+H]+.

Workup

  1. customthe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (15 mL)
  5. washthe combined organic layers were washed with water (10 mL), brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc23c9766ef74ee6b2f84c0ca51b6000
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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