Sodium hydride → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 448582

反応式

HRID 448582 の反応式
[H-].[Na+].[CH3:3][S:4]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH2:11][CH2:10]2)(=[O:6])=[O:5].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[CH:35]=[C:34](Cl)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.[Cl-].[Na+].O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[CH:35]=[C:34]([N:12]3[C:13]4[C:9](=[CH:8][C:7]([S:4]([CH3:3])(=[O:6])=[O:5])=[CH:15][CH:14]=4)[CH2:10][CH2:11]3)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 27361365-(Methanesulfonyl)-2,3-dihydro-1H-indoleHCID 22309472tert-Butyl 4-[(6-chloropyrimidin-4-yl)amino]piperidine-1-carboxylate

生成物 1

HCID 580741254-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester収率 62.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of NaH (0.62 g, 15.5 mmol, 60% NaH) in 40 mL of DMF, 5-methanesulfonyl-2,3-dihydro-1H-indole (1.9 g, 9.63 mmol) was added and the mixture was stirred at room temperature for 30 minutes. 17a (3.09 g, 9.88 mmol) was added in DMF and the mixture was heated at 85° C. for 17 h. After cooling to room temperature, brine was added (200 mL) and the mixture was extracted with DCM (200 mL then 3×500 mL). The combined extracts were washed with brine (3×100 mL), dried, filtered and evaporated. The residue was purified by flash chromatography (eluent: 25 to 100% EtOAc in hexane with 0.1% triethylamine) to afford 2.83 g (62%) of 17b.

後処理

  1. temperaturethe mixture was heated at 85° C. for 17 h
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with DCM (200 mL
  4. washThe combined extracts were washed with brine (3×100 mL)
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography (eluent: 25 to 100% EtOAc in hexane with 0.1% triethylamine)

出典と根拠

ORDレコード
ord-193c47e56d1b44f9927c0f14fe6990bf
出典データセット
uspto-grants-2013_07
特許番号
US08481731B2

関連ノート

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