Trifluoroacetic acid → 1-(4-(2-(5-((Azetidin-3-yloxy)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea

HRID 1400932ノート

反応式

HRID 1400932 の反応式
[CH:1]1([NH:4][C:5](=[O:43])[NH:6][C:7]2[CH:41]=[CH:40][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][O:28][CH:29]6[CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]6)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:42])[CH:8]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:31]1[CH2:30][CH:29]([O:28][CH2:27][C:24]2[CH:23]=[CH:22][C:21]([C:19]3[S:20][C:13]4[C:14](=[N:15][CH:16]=[CH:17][C:12]=4[O:11][C:10]4[CH:40]=[CH:41][C:7]([NH:6][C:5]([NH:4][CH:1]5[CH2:2][CH2:3]5)=[O:43])=[CH:8][C:9]=4[F:42])[CH:18]=3)=[N:26][CH:25]=2)[CH2:32]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 67443636Tert-butyl 3-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methoxy)azetidine-1-carboxylate

生成物 1

HCID 674417991-(4-(2-(5-((Azetidin-3-yloxy)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea収率 84%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a suspension of 404 (221 mg, 0.365 mmol) in DCM (5 mL) was added TFA (1 mL) and the reaction mixture was stirred for 4 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 25 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 10/90 to 30/70), to afford the title compound 405 (155 mg, 84% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.77 (s, 1H), 8.55 (brd, J=1.6 Hz, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.35 (s, 1H), 8.27 (d, J=7.2 Hz, 1H), 7.91 (dd, J=8.0, 2.4 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.24-7.18 (m, 1H), 6.65 (d, J=5.2 Hz, 1H), 6.62 (brd, J=2.8 Hz, 1H), 4.48 (s, 2H), 4.40-4.41 (m, 1H), 3.56-3.49 (m, 2H), 3.47-3.50 (m, 2H), 2.58-2.51 (m, 1H), 0.68-0.62 (m, 2H), 0.47-0.41 (m, 2H). MS (m/z): 506.14 (M+H).

後処理

  1. concentrationthen concentrated
  2. additiondiluted with water and 1M NaOH to pH 11
  3. filtrationThe solid was collected by filtration
  4. washrinsed with water
  5. customdried
  6. customThe residue was purified by Biotage (SNAP 25 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 10/90 to 30/70)

出典と根拠

ORDレコード
ord-6bc178e0ac0a459c8e85c53209121326
出典データセット
uspto-grants-2014_12
特許番号
US08906852B2

反応ノート

読み込み中…