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

HRID 592467Notes

Reaction equation

HRID 592467 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([NH:12][C:13]3[N:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH:27]([CH3:31])[C:28]([NH2:30])=[O:29])[C:16]([C:32]([F:35])([F:34])[F:33])=[CH:15][N:14]=3)[CH:9]=[N:8]2)[CH2:3][CH2:2]1.C=O.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:38][N:1]1[CH2:2][CH2:3][CH:4]([N:7]2[CH:11]=[C:10]([NH:12][C:13]3[N:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH:27]([CH3:31])[C:28]([NH2:30])=[O:29])[C:16]([C:32]([F:34])([F:33])[F:35])=[CH:15][N:14]=3)[CH:9]=[N:8]2)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 732951232-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-ylethyl)phenyl)propanamide

Product 1

HCID 732952922-(2-(2-(2-((1-(1-Methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamideYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-(2-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamide 56 (1.14 g, 2.33 mmol) in MeOH (40 mL) was added formaldehyde solution (37% in water, 0.52 mL, 7.0 mmol) and sodium triacetoxyborohydride (1.98 g, 9.33 mmol) under a nitrogen atmosphere. The mixture was stirred at room temperature for 4 hours before concentrating under reduced pressure. The mixture was diluted with sat. aq. NaHCO3 (75 mL) and the aqueous phase was extracted with EtOAc (3×50 mL). The combined organics were washed with brine and dried (MgSO4) before the solvent was removed in vacuo to give the product as a white solid (1.05 g, 90%). 1H NMR (400 MHz, d6-DMSO) δ 10.22-10.09 (m, 1H), 8.69-8.55 (m, 1H), 8.04-7.95 (m, 1H), 7.58 (s, 1H), 7.43-7.35 (m, 1H), 7.29-7.12 (m, 4H), 6.96-6.84 (m, 1H), 4.13-4.01 (m, 1H), 3.90-3.79 (m, 1H), 3.27-2.88 (m, 4H), 2.83 (d, J=10.0 Hz, 2H), 2.19 (s, 3H), 2.07-1.87 (m, 6H), 1.33 (d, J=6.8 Hz, 3H). LCMS-D: rt 3.03 min; m/z 502 [M+H]+.

Workup

  1. concentrationbefore concentrating under reduced pressure
  2. additionThe mixture was diluted with sat. aq. NaHCO3 (75 mL)
  3. extractionthe aqueous phase was extracted with EtOAc (3×50 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4) before the solvent
  6. customwas removed in vacuo

Sources & evidence

ORD record
ord-015946f84c824fb881a58d2673a36570
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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