Dichloromethane → (E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid hydrochloride

HRID 1362085ノート

反応式

HRID 1362085 の反応式
C([O:5][C:6](=[O:31])/[CH:7]=[CH:8]/[C:9]1[CH:30]=[N:29][C:12]2[NH:13][C:14](=[O:28])[CH2:15][N:16]([CH2:18][C:19]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[O:20])[CH2:17][C:11]=2[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:40]>>[ClH:40].[CH3:27][N:24]1[CH2:23][CH2:22][N:21]([C:19](=[O:20])[CH2:18][N:16]2[CH2:17][C:11]3[CH:10]=[C:9](/[CH:8]=[CH:7]/[C:6]([OH:31])=[O:5])[CH:30]=[N:29][C:12]=3[NH:13][C:14](=[O:28])[CH2:15]2)[CH2:26][CH2:25]1

参加物

4

反応物 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59456905(E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid tert-butyl ester

生成物 1

HCID 66967110(E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid hydrochloride

実験手順

A suspension of (E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid tert-butyl ester (1.12 g, 2.61 mmol) in CH2Cl2 (10 mL) was treated with TFA (10 mL). After stirring at room temperature for 35 min, the solution was concentrated in vacuo. The resulting oil was treated with anhydrous HCl (20 mL of a 4.0 M solution in dioxane, 80 mmol) and the resulting mixture was sonicated for 1 h. The mixture was diluted with Et2O (50 mL) and sonicated for 10 min. The solid was isolated by filtration, washed with Et2O and dried under vacuum at 50° C. for 4 h to give the title compound (1.72 g, quantitative) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 11.60 (br s, 1H), 11.09 (br s, 1H), 8.82 (s, 1H), 8.47 (s, 1H), 7.66 (d, J=19.9 Hz, 1H), 6.65 (d, J=16.1 Hz, 1H), 4.43-4.40 (m, 2H), 4.31 (br s, 2H), 3.95-3.91 (m, 1H), 3.84 (br s, 2H), 3.56 (s, 4H), 3.42 (br s, 2H), 3.23-2.97 (m, 2H), 2.76 (d, J=4.1 Hz, 3H); MS (ESI) m/e 374 (M+H)+.

後処理

  1. concentrationthe solution was concentrated in vacuo
  2. additionThe resulting oil was treated with anhydrous HCl (20 mL of a 4.0 M solution in dioxane, 80 mmol) and the resulting mixture
  3. customwas sonicated for 1 h
  4. additionThe mixture was diluted with Et2O (50 mL)
  5. customsonicated for 10 min
  6. customThe solid was isolated by filtration
  7. washwashed with Et2O
  8. customdried under vacuum at 50° C. for 4 h

出典と根拠

ORDレコード
ord-d1b504d334ab464eb7943cc847769458
出典データセット
uspto-grants-2011_02
特許番号
US07879872B2

反応ノート

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