Diisopropylethylamine → (S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (5-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-phenyl)-amide

HRID 1697881Notes

Reaction equation

HRID 1697881 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C:12](=[O:14])[NH:11][CH:10]=[C:9]2[C:15]([OH:17])=O)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:51]([Si:55]([CH3:74])([CH3:73])[O:56][CH2:57][CH2:58][N:59]1[C:63]([CH3:64])=[CH:62][C:61]([C:65]2[CH:66]=[CH:67][C:68]([CH3:72])=[C:69]([NH2:71])[CH:70]=2)=[N:60]1)([CH3:54])([CH3:53])[CH3:52]>CN1C(=O)CCC1.O>[C:51]([Si:55]([CH3:74])([CH3:73])[O:56][CH2:57][CH2:58][N:59]1[C:63]([CH3:64])=[CH:62][C:61]([C:65]2[CH:66]=[CH:67][C:68]([CH3:72])=[C:69]([NH:71][C:15]([C:9]3[C@H:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH2:13][C:12](=[O:14])[NH:11][CH:10]=3)=[O:17])[CH:70]=2)=[N:60]1)([CH3:53])([CH3:52])[CH3:54]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45378709HCID 45378709, compoundHCID 66955104HCID 66955104, compound

Product 1

HCID 67277422(S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (5-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-phenyl)-amideYield 40.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (138 mg), N,N-Diisopropylethylamine (155 mg) and HATU (152 mg) in NMP (1 ml) was stirred at room temperature for 10 minutes. A solution of 5-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-phenylamine (94 mg) in NMP (1 ml) was added, and the reaction mixture was stirred for 16 hours at room temperature. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by “flash chromatography” (0 to 5% MeOH in CH2Cl2) to give 62.2 mg of (S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (5-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-phenyl)-amide as an amorphous solid.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by “flash chromatography” (0 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-aef0caf7e06b4e2697446b69a7d7b519
Source dataset
uspto-grants-2012_04
Patent number
US08163929B2

Reaction notes

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