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

HRID 1711436
ノート
印刷プレビュー

反応式

HRID 1711436 の反応式
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)[CH2:16][C:15]2[C:10](=[CH:11][C:12]([OH:42])=[C:13]([NH2:41])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[CH:49]([C:53]1[CH:58]=[CH:57][C:56]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][C:64]([Cl:67])=[C:63]([Cl:68])[CH:62]=2)=[CH:55][CH:54]=1)[C:50](Cl)=[O:51].C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:29]=[CH:30][C:31]([C:34]#[N:35])=[CH:32][CH:33]=3)=[CH:24][CH:23]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[C:12]([O:42][C@@H:49]([C:53]4[CH:58]=[CH:57][C:56]([O:59][CH2:60][C:61]5[CH:66]=[CH:65][C:64]([Cl:67])=[C:63]([Cl:68])[CH:62]=5)=[CH:55][CH:54]=4)[C:50](=[O:51])[NH:41]3)=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 593375102-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chlorideHCID 66922945(S)-6-amino-3-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-7-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

生成物 1

HCID 66922703
(S)-7-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester
収率 61.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒2 回

実験手順

(S)-6-amino-3-[(S)-2-(4′-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-7-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.75 mmol) was dissolved in 5 mL EtOAc, 10 mL water and 15 g sodium bicarbonate added. 2-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chloride (1.93 mmol) in 5 mL EtOAc was added to the mixture. The resulting mixture stirred at r.t. for 1.5 h. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The resulting residue was dissolved in 5 mL DMF and potassium carbonate (8.75 mmol) added. The reaction stirred at r.t. for 3 h and was poured onto ethyl acetate and water. The organic was dried and concentrated. The residue was purified over silica gel (-hexanes-ethyl acetate) to provide (S)-7-[(S)-2-(4′-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester (931 mg). LC-MS (m/z) 862.

後処理

  1. washThe organic layer was washed with brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was dissolved in 5 mL DMF
  5. stirringThe reaction stirred at r.t. for 3 h
  6. customThe organic was dried
  7. concentrationconcentrated
  8. customThe residue was purified over silica gel (-hexanes-ethyl acetate)

出典と根拠

ORDレコード
ord-82f8a7f3f9df44639f71888e4e207563
出典データセット
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07790714B2

反応ノート

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