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 1400920ノート

反応式

HRID 1400920 の反応式
[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

参加物

4

反応物 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

生成物 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)urea収率 74.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-9c0ab404e20d443dbb11263a7b574bc2
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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