Isoquinolin-3-Amine → Morpholine-4-carboxylic acid (4-{[2-(isoquinolin-3-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide

HRID 2100416

반응식

HRID 2100416 반응식
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C[O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][CH2:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[O:31])[CH:24]=1.C[Al](C)C>ClCCCl.C(=O)([O-])O.[Na+]>[CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[C:2]([NH:1][C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][CH2:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)=[O:31])[CH:24]=2)=[O:13])[N:3]=1

참가 물질

6

반응물 3

HCID 311869Isoquinolin-3-AmineHCID 16682925TrimethylaluminumHCID 57798919HCID 57798919, 화합물

생성물 1

HCID 11612737Morpholine-4-carboxylic acid (4-{[2-(isoquinolin-3-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide수율 32%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
120 °C

실험 절차

To a stirred solution of 3-aminoisoquinoline (75 mg, 0.52 mmol) and 2-({2-[(morpholine-4-carbonyl)-amino]-pyridin-4-ylmethyl}-amino)-benzoic acid methyl ester (149 mg, 0.40 mmol) in DCE (6 mL) at 0° C., under argon, was added trimethylaluminium (2M in toluene, 0.4 mL, 0.8 mmol). The reaction was heated at 120° C. (bath temperature) for 3 hours. On cooling the reaction was diluted with aqueous sodium hydrogencarbonate solution and extracted with dichloromethane. The organic phase was washed with water, dried and concentrated in vacuo. The residue was purified by chromatography on Isolute® flash NH2 (Separtis) (Eluant: EtOAc) to give morpholine-4-carboxylic acid (4-{[2-(isoquinolin-3-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide (60 mg, 32%) as a resin; 1H-NMR (300 MHz, d6-DMSO) 10.69 (1H, s), 9.21 (1H, s), 9.18 (1H, s), 8.60 (1H, s), 8.16-8.20 (2H, m), 8.10 (1H, d), 7.96 (1H, d), 7.90 (1H, d), 7.82 (1H, d), 7.75 (1H, t), 7.57 (1H, t), 7.28 (1H, t), 6.98 (1H, d), 6.63 (1H, t), 6.58 (1H, d), 4.48 (2H, d), 3.55-3.59 (4H, m), 3.41-3.45 (4H, m); m/z (ES+) 483 [M+H]+, 242.

후처리

  1. temperatureOn cooling the reaction
  2. extractionextracted with dichloromethane
  3. washThe organic phase was washed with water
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on Isolute® flash NH2 (Separtis) (Eluant: EtOAc)

출처 및 근거

ORD 기록
ord-2d081de20bb34e8f876f4280e5410b34
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572794B2

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