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 1838872노트

반응식

HRID 1838872 반응식
[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]

참가 물질

4

반응물 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

생성물 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 ester수율 45%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-085982766d2c4cd791a52c9d47ee345a
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06677337B2

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