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1-Methylimidazole → 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-oxoindolin-5-yl)piperidine-3-carboxamide

HRID 1410077
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HRID 1410077 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([OH:26])=O)[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH2:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35](=[O:40])[CH2:34]2.CN1C=CN=C1.CCN=C=NCCCN(C)C>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:30][C:31]4[CH:32]=[C:33]5[C:37](=[CH:38][CH:39]=4)[NH:36][C:35](=[O:40])[CH2:34]5)=[O:26])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
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참가 물질

6

반응물 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27732135-Amino-2-oxindoleHCID 683795141-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid

생성물 1

HCID 665498981-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-oxoindolin-5-yl)piperidine-3-carboxamide수율 51.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (100 mg, 0.24 mmol) and 5-aminoindolin-2-one (36 mg, 0.24 mmol) in dichloromethane (20 mL) were added 1-methyl-1H-imidazole (79 mg, 0.96 mmol) and EDCI (183 mg, 0.96 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 15 hours, the solid was collected by filtration and washed with methanol (4 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-oxoindolin-5-yl)piperidine-3-carboxamide as a orange solid (68 mg, 51.8%). 1H NMR (300 MHz, DMSO): δ 10.31 (s, 1H), 9.87 (s, 1H), 9.67 (s, 1H), 8.86 (s, 1H), 7.68 (d, 1H, J=2.4 Hz), 7.53 (s, 1H), 7.37 (s, 1H), 7.35 (s, 1H), 6.83-6.81 (m, 1H), 6.75 (d, 1H, J=8.4 Hz), 4.82-4.67 (m, 2H), 3.71-3.65 (m, 6H), 3.48 (s, 2H), 3.12-2.95 (m, 2H), 1.98-1.74 (m, 5H). LC-MS: 546 [M+H]+, tR=1.493 min. HPLC: 98.74% at 214 nm, 98.67% at 25 4 nm, tR=3.60 min.

후처리

  1. filtrationthe solid was collected by filtration
  2. washwashed with methanol (4 mL)

출처 및 근거

ORD 기록
ord-a280d9aab2ee4433a1681fb4eb03d8d5
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08921383B2

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