Formaldehyde → HCID 73295629, compound

HRID 592486Notes

Reaction equation

HRID 592486 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[C:27]4([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]4)[C:16]([C:33]([F:36])([F:35])[F:34])=[CH:15][N:14]=3)[CH:9]=[N:8]2)[CH2:3][CH2:2]1.C=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:39][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[C:27]4([C:30]([NH2:32])=[O:31])[CH2:28][CH2:29]4)[C:16]([C:33]([F:35])([F:34])[F:36])=[CH:15][N:14]=3)[CH:9]=[N:8]2)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 73295468HCID 73295468, compound

Product 1

HCID 73295629HCID 73295629, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1-(2-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide 66 (0.081 g, 0.16 mmol) and formaldehyde (37 wt % in H2O; 36 μL, 0.49 mmol) in MeOH (5 mL) was stirred at room temperature for 10 minutes. Sodium triacetoxyborohydride (0.137 g, 0.649 mmol) was then added and stirring was continued for 3 hours at room temperature. The volatiles were removed in vacuo and sat. aq. NaHCO3 (20 mL) was added to the residue. The aqueous phase was extracted with EtOAc (3×20 mL) and the combined organics were washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The yellow residue was taken up in MeOH and loaded onto an SCX cartridge (10 g). The column was eluted with 5 column volumes of MeOH and then 5 column volumes of 2% v/v aqueous ammonia in MeOH to release the amine product. The solvent was evaporated under reduced pressure, the residue was taken up in DCM and a solid was precipitated by the addition of petroleum benzine 40-60° C. The solid was isolated by filtration and air dried to give the title compound 67 as a yellow solid (0.048 g, 58%). LCMS-A: rt 4.82 min; m/z 514 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for 3 hours at room temperature
  3. customThe volatiles were removed in vacuo and sat. aq. NaHCO3 (20 mL)
  4. additionwas added to the residue
  5. extractionThe aqueous phase was extracted with EtOAc (3×20 mL)
  6. washthe combined organics were washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent was removed in vacuo
  9. washThe column was eluted with 5 column volumes of MeOH
  10. customThe solvent was evaporated under reduced pressure
  11. customa solid was precipitated by the addition of petroleum benzine 40-60° C
  12. customThe solid was isolated by filtration and air
  13. customdried

Sources & evidence

ORD record
ord-5104129987bb4021908fe2f7b74b1995
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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