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

HRID 1410082

反応式

HRID 1410082 の反応式
[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)[C:36](=[O:40])[NH:35][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)[C:36](=[O:40])[NH:35][CH2:34]5)=[O:26])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

参加物

6

反応物 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 219562395-Amino-2,3-dihydro-isoindol-1-oneHCID 683795141-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid

生成物 1

HCID 665498991-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1-oxoisoindolin-5-yl)piperidine-3-carboxamide収率 51.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (70 mg, 0.17 mmol) and 5-aminoisoindolin-1-one (25 mg, 0.17 mmol) in dichloromethane (15 mL) were added the solution of 1-methyl-1H-imidazole (55 mg, 0.68 mmol) and EDCI (129 mg, 0.68 mmol) in dichloromethane (5 mL), the reaction mixture was stirred at room temperature for 24 hours, the solvent was removed in vacuo, then methanol (5 mL) was added, the precipitate was collected by filtration and washed with methanol (3 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1-oxoisoindolin-5-yl)piperidine-3-carboxamide (48 mg, 51.8%) as a brown solid. 1H NMR (300 MHz, DMSO): δ 10.29 (s, 1H), 9.64 (s, 1H), 8.84 (s, 1H), 8.38 (s, 1H), 7.96 (s, 1H), 7.64-7.53 (m, 3H), 7.33 (dd, 1H, J1=8.4 Hz, J2=1.8 Hz), 6.80 (brs, 1H), 4.81-4.63 (m, 2H), 4.33 (s, 2H), 3.68 (s, 3H), 3.59 (s, 3H), 3.14-2.92 (m, 2H), 2.65-2.60 (m, 1H), 2.04-2.00 (m, 1H), 1.81-1.69 (m, 2H), 1.49-1.45 (m, 1H). LC-MS: 545.9 [M+H]+, tR=1.42 min. HPLC: 99.69% at 214 nm, 99.44% at 254 nm, tR=4.87 min.

後処理

  1. customthe solvent was removed in vacuo
  2. additionmethanol (5 mL) was added
  3. filtrationthe precipitate was collected by filtration
  4. washwashed with methanol (3 mL)

出典と根拠

ORDレコード
ord-100c0df02bce4dc183d6418741047b4e
出典データセット
uspto-grants-2014_12
特許番号
US08921383B2

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