1,1'-Carbonyldiimidazole → 3-[[[[4'-[[2-[(tert-butoxycarbonyl)-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate

HRID 2078669

反応式

HRID 2078669 の反応式
[C:1]([O:5][C:6]([N:8]([CH2:32][C@@H:33]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=1)[OH:34])[CH2:9][CH2:10][NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([OH:26])=O)=[C:20]([O:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH:19]=2)=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.N1CCCN2CCCCCC=12.[C:65]([O:68][CH2:69][CH2:70][CH2:71][S:72]([NH2:75])(=[O:74])=[O:73])(=[O:67])[CH3:66]>CN(C)C=O>[C:65]([O:68][CH2:69][CH2:70][CH2:71][S:72]([NH:75][C:24]([C:21]1[CH:22]=[CH:23][C:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:11][CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:32][C@@H:33]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=3)[OH:34])=[CH:17][CH:16]=2)=[CH:19][C:20]=1[O:27][CH2:28][CH:29]([CH3:30])[CH3:31])=[O:26])(=[O:73])=[O:74])(=[O:67])[CH3:66]

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 106074883-(Aminosulfonyl)propyl acetateHCID 67097817HCID 67097817、化合物

生成物 1

HCID 670975243-[[[[4'-[[2-[(tert-butoxycarbonyl)-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate収率 44.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylcarboxylic acid (60.0 mg) in N,N-dimethylformamide (0.450 ml) was added 1,1′-carbonylbis-1H-imidazole (18.3 mg) and the mixture was stirred at room temperature for 1.5 hours under nitrogen atmosphere. To the mixture were added 2,3,4,6,7,8,9,10-octahydropyrimido-[1,2-a]azepine (0.0185 ml) and a solution of 3-(aminosulfonyl)propyl acetate (22.4 mg) in N,N-dimethylformamide (0.300 ml) and the mixture was stirred at room temperature for 2 days. The reaction mixture was warmed to 120° C. and stirred at the same temperature for 2 hours. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate, washed with water and brine and dried over magnesium sulfate. Filtration followed by evaporation gave the crude product which was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/3 to 1/1) to give 3-[[[[4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate (34.1 mg) as a yellow paste.

後処理

  1. temperatureThe reaction mixture was warmed to 120° C.
  2. stirringstirred at the same temperature for 2 hours
  3. temperatureAfter cooling to room temperature
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration
  8. customfollowed by evaporation
  9. customgave the crude product which
  10. customwas purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/3 to 1/1)

出典と根拠

ORDレコード
ord-f1f6816d1790498d9849d7cf4023712a
出典データセット
uspto-grants-2011_04
特許番号
US07928264B2

関連ノート

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