Diisopropylethylamine → Ethyl 5-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)pentanoate

HRID 1400950노트

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HRID 1400950 반응식
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][N:31]6[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]6)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.Br[CH:48]([CH3:56])[CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52]>CS(C)=O.CCOC(C)=O.CO.C(Cl)Cl>[OH-:6].[NH4+:4].[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]=[CH:26][C:27]([CH2:30][N:31]6[CH2:32][CH2:33][N:34]([CH2:56][CH2:48][CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:35][CH2:36]6)=[CH:28][CH:29]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)[CH2:3][CH2:2]1

참가 물질

8

반응물 3

HCID 81531DiisopropylethylamineHCID 316888Ethyl 4-bromopentanoateHCID 674423881-Cyclopropyl-3-(3-fluoro-4-(2-(5-(piperazin-1-ylmethyl)pyridin-2-yl)thieno[3,2-b]-pyridin-7-yloxy)phenyl)urea

생성물 2

HCID 14923Ammonium Hydroxide수율 2%HCID 67443956Ethyl 5-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)pentanoate수율 74.4%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매HCID 21226129Dichloromethane methanol용매

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온도
52.5 °C

실험 절차

To a stirred solution of 49 (200 mg, 0.39 mmol, scheme 15) and DIPEA (202 μl, 1.16 mmol) in DMSO (5 ml) at rt under nitrogen was added ethyl 4-bromovalerate (85 μl, 0.58 mmol), and the reaction mixture was heated at 50-55° C. for 1 h, then at rt. The reaction mixture was diluted with AcOEt, and successively washed with water, a saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified twice by Biotage (SiliaFlash 25 g cartridge: 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 10/90 over 20 CV, then 10/90 to 15/85 over 10 CV; Snap 25 g cartridge: 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 15/85 over 30 CV) to afford the desired product 517 (94 mg, 0.145 mmol, 37% yield) as a colorless sticky solid. MS (m/z): 647.75 (M+H).

후처리

  1. customat rt
  2. washsuccessively washed with water
  3. dry with materiala saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified twice by Biotage (SiliaFlash 25 g cartridge

출처 및 근거

ORD 기록
ord-867b3d0933624afab5e0627a0e6c4f4c
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906852B2

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