4-Methylpyrazole → 4-[3'-Fluoro-5'-(4-methyl-pyrazol-1-ylmethyl)-2,3,5,6-tetrahydro-[1,2]bipyridinyl-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 2066865ノート

反応式

HRID 2066865 の反応式
S(Cl)(C)(=O)=O.[CH:6]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([O:18][N:19]=[C:20]2[CH2:25][CH2:24][N:23]([C:26]3[C:31]([F:32])=[CH:30][C:29]([CH2:33]O)=[CH:28][N:27]=3)[CH2:22][CH2:21]2)[CH2:14][CH2:13]1)=[O:11])([CH3:8])[CH3:7].C(N(CC)CC)C.[CH3:42][C:43]1[CH:44]=[N:45][NH:46][CH:47]=1.[H-].[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH:6]([O:9][C:10]([N:12]1[CH2:13][CH2:14][CH:15]([O:18][N:19]=[C:20]2[CH2:25][CH2:24][N:23]([C:26]3[C:31]([F:32])=[CH:30][C:29]([CH2:33][N:45]4[CH:44]=[C:43]([CH3:42])[CH:47]=[N:46]4)=[CH:28][N:27]=3)[CH2:22][CH2:21]2)[CH2:16][CH2:17]1)=[O:11])([CH3:7])[CH3:8]

参加物

9

反応物 5

HCID 34064-MethylpyrazoleHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 583336054-(3'-Fluoro-5'-hydroxymethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl ester

生成物 1

HCID 583336124-[3'-Fluoro-5'-(4-methyl-pyrazol-1-ylmethyl)-2,3,5,6-tetrahydro-[1,2]bipyridinyl-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
100 °C

実験手順

Mesyl chloride (96 μL, 1.2 mmol) was added to an ice cooled solution of 53-1 (0.25 g, 0.62 mmol) and triethylamine (0.26 mL, 1.9 mmol) in 5 mL of DCM. After 2 h, the mixture was diluted with DCM (30 mL), washed with brine (15 mL) and water (15 mL), dried and concentrated under vacuum. The residue was taken up in DMF and added to a mixture of 4-methyl-1H-pyrazole (0.8 mmol) and sodium hydride (30 mg, 60%, 0.8 mmol) in DMF which had been pre-stirred for 5 minutes. The mixture was heated to 100° C. for 2 h then allowed to cool down to room temperature, diluted with water (1.5 mL) and extracted with DCM (2 mL). The organic layer was concentrated under a stream of nitrogen, the residue was taken up in methanol and the mixture was purified by HPLC to afford 54-1: LC-MS 473.2 (MH+).

後処理

  1. washwashed with brine (15 mL) and water (15 mL)
  2. customdried
  3. concentrationconcentrated under vacuum
  4. temperatureto cool down to room temperature
  5. extractionextracted with DCM (2 mL)
  6. concentrationThe organic layer was concentrated under a stream of nitrogen
  7. customthe mixture was purified by HPLC
  8. customto afford 54-1

出典と根拠

ORDレコード
ord-bd6c55ddffea460dadea2a5b42441102
出典データセット
uspto-grants-2012_10
特許番号
US08293729B2

反応ノート

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