N,N-Diethyl-2-propanamine → 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-yl)urea

HRID 1918086노트

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HRID 1918086 반응식
[F:1][C:2]([F:28])([C:7]1[CH:11]=[C:10]([NH:12][C:13](=[O:21])OC2C=CC=CC=2)[N:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:8]=1)[C:3]([F:6])([F:5])[F:4].[CH3:29][O:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][C:40]=1[O:41][CH3:42])[N:37]=[CH:36][N:35]=[C:34]2[O:43][C:44]1[CH:45]=[C:46]([CH:48]=[CH:49][CH:50]=1)[NH2:47].C(N(C(C)C)CC)C>C1COCC1>[CH3:29][O:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][C:40]=1[O:41][CH3:42])[N:37]=[CH:36][N:35]=[C:34]2[O:43][C:44]1[CH:45]=[C:46]([NH:47][C:13]([NH:12][C:10]2[N:9]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:8]=[C:7]([C:2]([F:1])([F:28])[C:3]([F:4])([F:6])[F:5])[CH:11]=2)=[O:21])[CH:48]=[CH:49][CH:50]=1

참가 물질

5

반응물 3

HCID 521913N,N-Diethyl-2-propanamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 86653532phenyl 3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-ylcarbamate

생성물 1

HCID 582679771-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-yl)urea수율 39.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

A stirred mixture of phenyl 3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-ylcarbamate (199 mg, 0.50 mmol), 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (prepared as described in Example 113A) (100 mg, 0.34 mmol), N,N-diethylisopropylamine (88 mg, 0.68 mmol) in THF (1 mL) was heated at 60° C. for 15 h. After cooling to rt, the reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane. The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to afford the crude product. Purification via preparative HPLC afforded 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-yl)urea (80 mg, 39%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.82 (s, 1H), 8.54 (s, 1H), 7.55-7.61 (m, 7H), 7.36-7.40 (m, 2H), 7.18 (m, 1H), 6.95 (m, 1H), 6.88 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); LC-MS (ESI) m/z 601 (M+H)+.

후처리

  1. temperatureAfter cooling to rt
  2. customthe reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude product
  7. customPurification via preparative HPLC

출처 및 근거

ORD 기록
ord-6881fac5d999447c88cac08980bce544
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618289B2

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