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 1400950ノート

反応式

HRID 1400950 の反応式
[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

参加物

8

反応物 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

生成物 2

HCID 14923Ammonium Hydroxide収率 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)pentanoate収率 74.4%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
52.5 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-867b3d0933624afab5e0627a0e6c4f4c
出典データセット
uspto-grants-2014_12
特許番号
US08906852B2

反応ノート

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