1-{(S)-2-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-piperidin-1-yl}-1-[4-(4-fluoro-phenyl)-1-methyl-1H-pyrazol-3-yl]-methanone → 2-[((S)-1-{1-[4-(4-Fluoro-phenyl)-1-methyl-1H-pyrazol-3-yl]-methanoyl}-piperidin-2-ylmethyl)-amino]-pyrimidine-5-carbonitrile

HRID 18108Notes

Reaction equation

HRID 18108 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][N:11]2[C:16]([C:18]2[C:22]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[CH:21][N:20]([CH3:30])[N:19]=2)=[O:17])=[N:6][CH:7]=1.[Cu][C:32]#[N:33]>CN1CCCC1=O.O>[F:29][C:26]1[CH:27]=[CH:28][C:23]([C:22]2[C:18]([C:16]([N:11]3[CH2:12][CH2:13][CH2:14][CH2:15][C@H:10]3[CH2:9][NH:8][C:5]3[N:4]=[CH:3][C:2]([C:32]#[N:33])=[CH:7][N:6]=3)=[O:17])=[N:19][N:20]([CH3:30])[CH:21]=2)=[CH:24][CH:25]=1

Participants

5

Reactant 2

HCID 670897601-{(S)-2-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-piperidin-1-yl}-1-[4-(4-fluoro-phenyl)-1-methyl-1H-pyrazol-3-yl]-methanoneHCID 178418546HCID 178418546, compound

Product 1

HCID 670900152-[((S)-1-{1-[4-(4-Fluoro-phenyl)-1-methyl-1H-pyrazol-3-yl]-methanoyl}-piperidin-2-ylmethyl)-amino]-pyrimidine-5-carbonitrileYield 6.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-{(S)-2-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-piperidin-1-yl}-1-[4-(4-fluoro-phenyl)-1-methyl-1H-pyrazol-3-yl]-methanone (0.35 g) in N-methylpyrrolidinone (10 ml) containing copper(I)cyanide (0.13 g) was heated to reflux for 5 h. The reaction mixture was diluted with water, filtered (Kieselguhr) and the filtrate extracted with ethyl acetate. The ethyl acetate phase was washed with water and brine, dried (MgSO4), filtered and solvent removed at reduced pressure. The residue was column chromatographed (silica gel; ethyl acetate:pentane 1:1→ethyl acetate eluant), the appropriate fractions combined and solvent removed at reduced pressure to give the title compound (0.019 g).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 h
  3. filtrationfiltered (Kieselguhr)
  4. extractionthe filtrate extracted with ethyl acetate
  5. washThe ethyl acetate phase was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customsolvent removed at reduced pressure
  9. customchromatographed (silica gel; ethyl acetate:pentane 1:1→ethyl acetate eluant)
  10. customsolvent removed at reduced pressure

Sources & evidence

ORD record
ord-1a6cd00fa6214fd5bf94e8469d78a90e
Source dataset
uspto-grants-2010_06
Patent number
US07741329B2

Reaction notes

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