Trifluoroacetic acid → 1-Cyclopropyl-3-(3-fluoro-4-(2-(5-(piperazin-1-ylmethyl)pyridin-2-yl)thieno[3,2-b]-pyridin-7-yloxy)phenyl)urea

HRID 1400812노트

반응식

HRID 1400812 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:26]=[CH:25][C:24]([CH2:27][N:28]6[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]6)=[CH:23][CH:22]=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[CH:22]=[CH:23][C:24]([CH2:27][N:28]6[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]6)=[CH:25][N:26]=5)[S:20][C:13]=34)=[C:9]([F:43])[CH:8]=2)=[O:44])[CH2:3][CH2:2]1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 67441338Tert-butyl 4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]-pyridin-2-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate

생성물 1

HCID 674423881-Cyclopropyl-3-(3-fluoro-4-(2-(5-(piperazin-1-ylmethyl)pyridin-2-yl)thieno[3,2-b]-pyridin-7-yloxy)phenyl)urea수율 100.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of 48 (1.456 g, 2.35 mmol) and TFA (15 mL) in DCM (50 mL) was stirred at RT for 5 hr. The TFA was removed by co-evaporation with DCM, the residue was diluted with water, and the pH was adjusted to ˜12-13 with 1N NaOH. The resultant suspension was sonicated for 15 min. The solid was collected by filtration, rinsed with water and dried under high vacuum to afford the title compound 49 (1.227 g, traces of TEA) as an off-white fluffy solid. 1H NMR (400 MHz. DMSO-d6) δ (ppm): 8.76 (bs, 1H), 8.54 (d, J=1.4 Hz, 1H), 8.52 (d, J=5.5 Hz, 1H), 8.32 (s, 1H), 8.24 (d, J=8.2 Hz, 1H), 7.85 (dd, J=8.1, 2.1 Hz, 1H), 7.73 (dd, J=13.5, 2.3 Hz, 1H), 7.38 (t, J=9.1 Hz, 1H), 7.20 (bd, J=10.2 Hz, 1H), 6.64 (d, J=5.5 Hz, 1H), 6.62 (bs, 1H), 3.58-3.48 (m, 2H), 2.73-2.64 (m, 4H), 2.59-2.52 (m, 1H), 2.38-2.25 (m, 4H), 0.69-0.62 (m, 2H), 0.46-0.40 (m, 2H), one NH is missing. MS (m/z): 519.6 (M+H).

후처리

  1. customThe TFA was removed by co-evaporation with DCM
  2. additionthe residue was diluted with water
  3. customThe resultant suspension was sonicated for 15 min
  4. filtrationThe solid was collected by filtration
  5. washrinsed with water
  6. customdried under high vacuum

출처 및 근거

ORD 기록
ord-b8d5cc5bd2ad4ea096ef42deb85690e9
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906852B2

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