Tert-butyl 3-{n-[(1r)-1-[(3,4-dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate → n-[(1r)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide

HRID 228085ノート

反応式

HRID 228085 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C@@H:10]([NH:30][C:31]([C@@H:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35][N:34]2C(OC(C)(C)C)=O)=[O:32])[C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C@@H:10]([NH:30][C:31]([C@@H:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35][NH:34]2)=[O:32])[C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

参加物

3

反応物 1

HCID 69077373Tert-butyl 3-{n-[(1r)-1-[(3,4-dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

生成物 1

HCID 10282776n-[(1r)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide収率 94.6%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

N-[(1R)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl)) carboxamide was prepared from tert-butyl 3-{N-[(1R)-1-[(3,4-dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Step 3) (590 mg, 0.80 mmol) according to the procedure for Preparation XVI. The resulting crude material was diluted with EtOAc and washed with satd NaHCO3 soln. The organic layer was separated, dried over Na2SO4, filtered and concentrated in vacuo. The material was purified by preparative HPLC to give the title compound (477 mg) as the TFA salt. MS (ESI, pos. ion) m/z: 630 (M+H), (ESI, neg. ion) m/z: 628 (M−H). Calc'd for C30H33Cl2N5O4S: 629.16. Anal. Calcd for C30H33Cl2N5O4S-1.5C2HF3O2-0.5H2O: C, 48.89; H, 4.41; N, 8.64; Cl, 8.75. Found C, 49.33; H, 4.47; N, 8.94; Cl, 8.61.

後処理

  1. washwashed with satd NaHCO3 soln
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was purified by preparative HPLC

出典と根拠

ORDレコード
ord-077267083b1e4d97895a8282feabb42b
出典データセット
uspto-grants-2009_07
特許番号
US07560460B2

反応ノート

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