Sodium hydride → 4-[4-(4-Fluorophenyl)-2-methyl-3-(2-methylsulfanyl-pyrimidin-4-yl)-5-oxo-2,5-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester

HRID 1838872ノート

反応式

HRID 1838872 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:27](=[O:36])[CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:15]([CH3:26])[C:16]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=2)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:27](=[O:36])[C:28]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=3)[N:15]2[CH3:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

4

反応物 2

HCID 24758Sodium hydrideHCID 600611404-{N-[2-(4-Fluoro-phenyl)-acetyl]-N'-methyl-N'-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 600611414-[4-(4-Fluorophenyl)-2-methyl-3-(2-methylsulfanyl-pyrimidin-4-yl)-5-oxo-2,5-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester収率 45%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a 0° C. solution of 4-{N-[2-(4-fluoro-phenyl)-acetyl]-N′-methyl-N′-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester, 17, (26.7 g, 51.7 mmol) in DMF (50 mL) is slowly added NaH (3.1 g of a 60% dispersion in mineral oil, 77.55 mmol). The reaction mixture is stirred for 0.5 h at 0° C. and then quenched with 1.0 N HCl. The aqueous layer is extracted threee times with CH2Cl2. The combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (100% EtOAc) affords 12 g (45% yield) of the desired product: 1H NMR (300 MHz, CDCl3) δ 8.50 (d, J=4.9 Hz, 1H), 7.35-7.29 (m, 2H), 7.02 (t, J=6.8 Hz, 2H), 6.85 (d, J=5.1 Hz, 1H), 4.42-4.32 (m, 3H), 3.28 (s, 3H), 2.88 (t, 12.8 Hz, 2H), 2.58 (s, 3H), 2.79-2.39 (m, 2H), 1.94 (d, J=11.7 Hz, 2H), 1.50 (s, 9H); ESI/MS: 500.3 (M+H).

後処理

  1. customTo a 0° C.
  2. customquenched with 1.0 N HCl
  3. extractionThe aqueous layer is extracted threee times with CH2Cl2
  4. dry with materialThe combined organic layers are dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification over silica (100% EtOAc)

出典と根拠

ORDレコード
ord-085982766d2c4cd791a52c9d47ee345a
出典データセット
uspto-grants-2004_01
特許番号
US06677337B2

反応ノート

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