Formaldehyde → 1-(2-(2-(2-((6-(1-Methylpiperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592490Notes

Reaction equation

HRID 592490 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N: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[C:28]4([C:31]([NH2:33])=[O:32])[CH2:30][CH2:29]4)[C:17]([C:34]([F:37])([F:36])[F:35])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C=O.[C:40](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:40][N:1]1[CH2:2][CH2:3][CH:4]([C:7]2[N: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[C:28]4([C:31]([NH2:33])=[O:32])[CH2:29][CH2:30]4)[C:17]([C:34]([F:35])([F:37])[F:36])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 732964281-(2-(2-(2-((6-(Piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 732956301-(2-(2-(2-((6-(1-Methylpiperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 29%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 1-(2-(2-(2-((6-(piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide 68 (0.069 g, 0.14 mmol) in anhydrous MeOH (2.0 mL) was added 37% aqueous formaldehyde (0.04 mL, 0.5 mmol) and sodium triacetoxyborohydride (0.147 g, 0.695 mmol). The mixture was stirred for 3 hours at room temperature under a nitrogen atmosphere and then quenched with sat. aq. NaHCO3 (30 mL). The aqueous phase was extracted with EtOAc (2×20 mL) and the combined organics were dried using a phase separation cartridge and concentrated in vacuo. Purification by prep-LCMS gave the title compound 69 (0.020 g, 29%) as the formic acid salt (2 equivs. determined by 1H NMR). LCMS-A: rt 4.802 min; m/z 525.3 [M+H]+.

Workup

  1. customquenched with sat. aq. NaHCO3 (30 mL)
  2. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  3. customthe combined organics were dried
  4. customa phase separation cartridge
  5. concentrationconcentrated in vacuo
  6. customPurification by prep-LCMS

Sources & evidence

ORD record
ord-55a3c0eb1cb94169a932e0374862d1d7
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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