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

HRID 1485277Notes

Reaction equation

HRID 1485277 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[N:20]=[C:19]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH2:29][C:30]([NH2:32])=[O:31])[C:18]([C:33]([F:36])([F:35])[F:34])=[CH:17][N:16]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:39][N:4]1[CH2:3][CH2:2][N:1]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([NH:14][C:15]3[N:20]=[C:19]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH2:29][C:30]([NH2:32])=[O:31])[C:18]([C:33]([F:34])([F:36])[F:35])=[CH:17][N:16]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601648052-(2-(2-(2-((4-(Piperazin-1-ylmethyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 601649112-(2-(2-(2-((4-((4-Methylpiperazin-1-yl)methyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-(2-(2-(2-((4-(Piperazin-1-ylmethyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (25) (11 mg, 0.022 mmol) was dissolved in methanol (1 mL). 37% Formaldehyde solution (7 μL) was added followed by sodium triacetoxyborohydride (24 mg, 0.11 mmol). The mixture was stirred vigorously at room temperature for two hours then concentrated. The residue was suspended in 10% sodium hydroxide (1 mL) and brine (2 mL) then extracted with ethyl acetate (5×2 mL). The combined ethyl acetate phases were washed with brine, dried over sodium sulfate, evaporated and the residue evaporated from DCM to give the title compound (36) (10.3 mg, 94% yield) as an off-white solid; 1H NMR (400 MHz, d4-MeOD) δ 8.46 (d, J=0.5 Hz, 1H), 7.60-7.54 (m, 2H), 7.20 (d, J=8.6 Hz, 2H), 7.18-7.13 (m, 1H), 7.13-7.07 (m, 3H), 3.57 (s, 2H), 3.46 (s, 2H), 3.06 (qd, J=6.8, 3.1 Hz, 2H), 3.01-2.94 (m, 2H), 2.54 (s, 8H), 2.29 (s, 3H). LCMS Method C: 4.70 min; m/z 513.2 [M+H+]+; m/z 511.0 [M−H]−.

Workup

  1. concentrationthen concentrated
  2. extractionbrine (2 mL) then extracted with ethyl acetate (5×2 mL)
  3. washThe combined ethyl acetate phases were washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customthe residue evaporated from DCM

Sources & evidence

ORD record
ord-6749b0d44ad0434caa4b089ea7a9426d
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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