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Pyridine → 1-(4-Chloro-5-(1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea

HRID 1430505
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HRID 1430505 반응식
[NH2:1][C:2]1[C:3]([F:29])=[CH:4][C:5]([Cl:28])=[C:6]([C:8]2[C:9](=[O:27])[N:10]([CH2:25][CH3:26])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH:19]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]2)[CH:12]=3)[CH:7]=1.N1C=CC=CC=1.[C:36]1([N:42]=[C:43]=[O:44])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C(Cl)Cl>[Cl:28][C:5]1[C:6]([C:8]2[C:9](=[O:27])[N:10]([CH2:25][CH3:26])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH:19]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]2)[CH:12]=3)=[CH:7][C:2]([NH:1][C:43]([NH:42][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:44])=[C:3]([F:29])[CH:4]=1
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참가 물질

5

반응물 3

HCID 1049PyridineHCID 7672Phenyl isocyanateHCID 867136543-(5-amino-2-chloro-4-fluorophenyl)-1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-1,6-naphthyridin-2(1H)-one

생성물 1

HCID 734424711-(4-Chloro-5-(1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea수율 8.4%

시약·촉매·용매 1

HCID 6344
Dichloromethane
용매

실험 절차

To a solution of 3-(5-amino-2-chloro-4-fluorophenyl)-1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-1,6-naphthyridin-2(1H)-one (500 mg, 1.20 mmol) and pyridine (140 mg, 1.8 mmol) in DCM (20 mL) was added phenyl isocyanate (215 mg, 1.8 mmol). The mixture was stirred at RT overnight, concentrated, and purified by prep-HPLC separation to give 1-(4-chloro-5-(1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea (53 mg, 8.4% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.67 (s, 1H), 8.40 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.73 (s, 1H), 7.53 (d, J=11.2 Hz, 1H), 7.41 (d, J=7.6 Hz, 2H), 7.28-7.23 (m, 3H), 6.98-6.95 (m, 1H), 6.35 (s, 1H), 4.39 (s, 1H), 4.11-4.09 (m, 2H), 2.77-2.71 (m, 1H), 2.65-2.61 (m, 1H), 2.44-2.36 (m, 2H), 2.26 (s, 3H), 2.23-2.20 (m, 1H), 1.68-1.62 (m, 1H), 1.64 (t, J=7.2 Hz, 3H).

후처리

  1. concentrationconcentrated
  2. custompurified by prep-HPLC separation

출처 및 근거

ORD 기록
ord-767084e292c449a6b965c90f11757466
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08940756B2

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