Acetyl chloride → (S)-1-acetyl-7-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

HRID 708657ノート

反応式

HRID 708657 の反応式
[C:1]([O:5][C:6]([N:8]1[CH:21]([C:22](=[O:44])[NH:23][C@H:24]([C:40]([O:42][CH3:43])=[O:41])[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)=[CH:28][CH:27]=2)[CH2:20][C:19]2[CH:18]=[C:17]3[C:12]([O:13][C@@H:14]([C:45]4[CH:50]=[CH:49][C:48]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=5)=[CH:47][CH:46]=4)[CH2:15][NH:16]3)=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:61](Cl)(=[O:63])[CH3:62].C(N(CC)CC)C.C(OCC)(=O)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH:21]([C:22](=[O:44])[NH:23][C@H:24]([C:40]([O:42][CH3:43])=[O:41])[CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)=[CH:30][CH:31]=2)[CH2:20][C:19]2[CH:18]=[C:17]3[C:12]([O:13][C@@H:14]([C:45]4[CH:46]=[CH:47][C:48]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=5)=[CH:49][CH:50]=4)[CH2:15][N:16]3[C:61](=[O:63])[CH3:62])=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 67250762(S)-7-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

生成物 1

HCID 67250498(S)-1-acetyl-7-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of (S)-7-[(S)-2-(4′-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester (85 mg) in DCM (5 mL) at 0° C. was treated with acetyl chloride, and triethylamine. The mixture was allowed to slowly warm to room temperature. After 3 hours, ethyl acetate was added and the organic layer was washed with 1N HCl. The organic layer was washed saturated sodium bicarbonate solution and brine, and dried over sodium sulfate. The solvent was removed under reduced pressure to give the crude amide. The residue was purified by flash chromatography (using hexanes/ethyl acetate, from 70:30 to 55:45, as an eluent) to give the product (76 mg).

後処理

  1. washthe organic layer was washed with 1N HCl
  2. washThe organic layer was washed saturated sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customto give the crude amide
  6. customThe residue was purified by flash chromatography (

出典と根拠

ORDレコード
ord-ad34ccb36d0441a8a0fc958b32ba4ef6
出典データセット
uspto-grants-2015_11
特許番号
US09175003B2

反応ノート

読み込み中…