Pyridine → tert-butyl 4-(2-(4-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate

HRID 1400919노트

반응식

HRID 1400919 반응식
[NH2:1][C:2]1[CH:37]=[CH:36][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:17]=[CH:18][N:19]([CH2:21][CH2:22][N:23]5[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]5)[CH:20]=4)[S:15][C:8]=23)=[C:4]([F:38])[CH:3]=1.[N:39]1[CH:44]=[CH:43][CH:42]=C[CH:40]=1.ClC(OC1C=CC=CC=1)=[O:47].C1(N)CC1>CN(C=O)C>[CH:44]1([NH:39][C:40](=[O:47])[NH:1][C:2]2[CH:37]=[CH:36][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[CH:13]=[C:14]([C:16]5[N:17]=[CH:18][N:19]([CH2:21][CH2:22][N:23]6[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH2:27][CH2:28]6)[CH:20]=5)[S:15][C:8]=34)=[C:4]([F:38])[CH:3]=2)[CH2:42][CH2:43]1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 67442156tert-butyl 4-(2-(4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate

생성물 1

HCID 67440535tert-butyl 4-(2-(4-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate수율 58%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a stirred solution of 306 (2.10 g, 3.90 mmol) and pyridine (631 μl, 4.68 mmol) in DMF (20 ml) at 0° C. was added phenyl chloroformate (587 μl, 4.68 mmol). After 45 min cyclopropylamine (687 μl, 9.75 mmol) was added at 0° C. and the reaction mixture was heated at 60° C. for 30 min. After cooling to RT the reaction mixture was quenched by addition of water and extracted with AcOEt. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 100 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 307 (1.4 g, 2.25 mmol, 58% yield) as a beige solid. MS (m/z): 622.33 (M+H).

후처리

  1. temperatureAfter cooling to RT the reaction mixture
  2. customwas quenched by addition of water
  3. extractionextracted with AcOEt
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 100 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)

출처 및 근거

ORD 기록
ord-b4a138c52212437cb8cabe4df1eded2b
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906852B2

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