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

HRID 1257214노트

반응식

HRID 1257214 반응식
[NH2:1][C:2]1[C:3]([F:30])=[CH:4][C:5]([Cl:29])=[C:6]([C:8]2[C:9](=[O:28])[N:10]([CH2:26][CH3:27])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[CH:12]=3)[CH:7]=1.N1C=CC=CC=1.[C:37]1([N:43]=[C:44]=[O:45])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C(Cl)Cl>[Cl:29][C:5]1[C:6]([C:8]2[C:9](=[O:28])[N:10]([CH2:26][CH3:27])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[CH:12]=3)=[CH:7][C:2]([NH:1][C:44]([NH:43][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:45])=[C:3]([F:30])[CH:4]=1

참가 물질

5

반응물 3

HCID 1049PyridineHCID 7672Phenyl isocyanateHCID 867136513-(5-amino-2-chloro-4-fluorophenyl)-1-ethyl-7-(1-methylpiperidin-4-ylamino)-1,6-naphthyridin-2(1H)-one

생성물 1

HCID 715850161-(4-Chloro-5-(1-ethyl-7-(1-methylpiperidin-4-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea수율 47%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of 3-(5-amino-2-chloro-4-fluorophenyl)-1-ethyl-7-(1-methylpiperidin-4-ylamino)-1,6-naphthyridin-2(1H)-one (200 mg, 0.465 mmol) and pyridine (70 mg, 0.95 mmol) in DCM (5 mL) was treated drop-wise with phenyl isocyanate (112 mg, 0.93 mmol) and stirred at RT under nitrogen overnight. The mixture was quenched with MeOH (5 mL), concentrated under reduced pressure and purified by prep-TLC separation to give 1-(4-chloro-5-(1-ethyl-7-(1-methylpiperidin-4-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea (120 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.16 (s, 1H), 8.72 (s, 1H), 8.39 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.71 (s, 1H), 7.51 (d, J=10.8 Hz, 1H), 7.42 (s, 1H), 7.40 (s, 1H), 7.26 (t, J=8.0 Hz, 2H), 7.02-6.94 (m, 2H), 6.33 (s, 1H), 4.11-4.05 (m, 2H), 3.81-3.78 (m, 1H), 2.78-2.75 (m, 2H), 2.20 (s, 3H), 2.12-2.05 (m, 2H), 1.90-1.88 (m, 2H), 1.52-1.47 (m, 2H), 1.21-1.18 (m, 3H); MS (ESI) m/z: 549.3 [M+H]+.

후처리

  1. customThe mixture was quenched with MeOH (5 mL)
  2. concentrationconcentrated under reduced pressure
  3. custompurified by prep-TLC separation

출처 및 근거

ORD 기록
ord-a93f0e1b2eee49bcb6511550381a451c
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461179B1

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