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 1697881ノート

反応式

HRID 1697881 の反応式
[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]

参加物

7

反応物 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、化合物HCID 66955104HCID 66955104、化合物

生成物 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)-amide収率 40.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-aef0caf7e06b4e2697446b69a7d7b519
出典データセット
uspto-grants-2012_04
特許番号
US08163929B2

反応ノート

読み込み中…