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

HRID 592442Notes

Reaction equation

HRID 592442 reaction equation
[CH3:1][C:2]1[C:3]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]2([C:32]([NH2:34])=[O:33])[CH2:31][CH2:30]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[N:6][CH:7]=1.C=O.[C:37](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C1CCCCC1>CO.C(Cl)Cl>[CH3:1][C:2]1[C:3]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]2([C:32]([NH2:34])=[O:33])[CH2:31][CH2:30]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([CH:15]3[CH2:20][CH2:19][N:18]([CH3:37])[CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8078CyclohexaneHCID 5049666Sodium triacetoxyborohydrideHCID 867123201-(2-(2-(5-Methyl-2-((6-(piperidin-4-yl)pyridin-3-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 732949451-(2-(2-(5-Methyl-2-((6-(1-methylpiperidin-4-yl)pyridin-3-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 41%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(2-(2-(5-methyl-2-((6-(piperidin-4-yl)pyridin-3-yl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A46 (0.121 g, 0.265 mmol) in MeOH (10 mL) was treated with formaldehyde solution (37% in water, 59 μL, 0.80 mmol) and sodium triacetoxyborohydride (0.225 g, 1.06 mmol) and stirred at room temperature for 3 hours. The mixture was concentrated in vacuo, aq. NaOH (2 M, ˜30 mL) was added and the aqueous phase was extracted with EtOAc (3×30 mL). The organics were combined, washed with brine, dried (MgSO4) and the solvent evaporated under reduced pressure to give a colourless oil. The oil was taken up in DCM and cyclohexane was added until a white precipitate formed. The suspension was sonicated for 10 minutes and the solid was isolated by vacuum filtration and dried under high vacuum for 4 hours to give the title compound 49 as a white solid (0.051 g, 41%). LCMS-D: rt 3.13 min; m/z 471 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo, aq. NaOH (2 M, ˜30 mL)
  2. additionwas added
  3. extractionthe aqueous phase was extracted with EtOAc (3×30 mL)
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent evaporated under reduced pressure
  7. customto give a colourless oil
  8. customformed
  9. customThe suspension was sonicated for 10 minutes
  10. customthe solid was isolated by vacuum filtration
  11. customdried under high vacuum for 4 hours

Sources & evidence

ORD record
ord-4fd1c35b29b54c128bac0d77050a5d81
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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