Trifluoroacetic acid → 1-cyclopropyl-3-(3-fluoro-4-(2-(1-(2-(piperazin-1-yl)ethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

HRID 1400920노트

반응식

HRID 1400920 반응식
[CH:1]1([NH:4][C:5](=[O:44])[NH:6][C:7]2[CH:42]=[CH:41][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:22]=[CH:23][N:24]([CH2:26][CH2:27][N:28]6[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]6)[CH:25]=5)[S:20][C:13]=34)=[C:9]([F:43])[CH:8]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([NH:4][C:5]([NH:6][C:7]2[CH:42]=[CH:41][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:22]=[CH:23][N:24]([CH2:26][CH2:27][N:28]6[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]6)[CH:25]=5)[S:20][C:13]=34)=[C:9]([F:43])[CH:8]=2)=[O:44])[CH2:2][CH2:3]1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 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-carboxylate

생성물 1

HCID 674442301-cyclopropyl-3-(3-fluoro-4-(2-(1-(2-(piperazin-1-yl)ethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea수율 74.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 307 (1.4 g, 2.25 mmol) in DCM (30 ml) was added TEA (2 mL) and the reaction mixture was stirred for 1 h. More TFA (3 mL) was added and the reaction mixture was stirred for an additional 3 h then concentrated, diluted with water and 1M NaOH to pH 11. The solid was collected by filtration, rinsed with water and dried. The residue was purified by Biotage (SNAP 80 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 35/65 over 30 CV), to afford the title compound 308 (870 mg, 1.67 mmol, 74% yield) as a beige solid.

후처리

  1. stirringthe reaction mixture was stirred for an additional 3 h
  2. concentrationthen concentrated
  3. additiondiluted with water and 1M NaOH to pH 11
  4. filtrationThe solid was collected by filtration
  5. washrinsed with water
  6. customdried
  7. customThe residue was purified by Biotage (SNAP 80 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 35/65 over 30 CV)

출처 및 근거

ORD 기록
ord-9c0ab404e20d443dbb11263a7b574bc2
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906852B2

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