Triethylamine → Benzyl (R)-3-(2-benzyloxycarbonylaminoethylsulfanyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)ureido]propionate

HRID 2040005ノート

反応式

HRID 2040005 の反応式
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C@@H:14]([CH2:25][S:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C(N(CC)CC)C.[NH2:47][C@@H:48]1[CH2:63][C:62]2=[CH:64][CH:65]=[C:59]([CH:60]=[CH:61]2)[O:58][CH2:57][CH2:56][CH2:55][CH2:54][O:53][CH2:52][C@H:51]([CH:66]([CH3:68])[CH3:67])[NH:50][C:49]1=[O:69]>CN(C=O)C>[CH2:33]([O:32][C:30]([NH:29][CH2:28][CH2:27][S:26][CH2:25][C@H:14]([NH:13][C:1]([NH:47][C@@H:48]1[CH2:63][C:62]2=[CH:61][CH:60]=[C:59]([CH:65]=[CH:64]2)[O:58][CH2:57][CH2:56][CH2:55][CH2:54][O:53][CH2:52][C@H:51]([CH:66]([CH3:67])[CH3:68])[NH:50][C:49]1=[O:69])=[O:2])[C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])=[O:31])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 58360483(9S,12R)-12-Amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-oneHCID 58360484Benzyl (R)-2-amino-3-(2-benzyloxycarbonylaminoethylsulfanyl)propionate

生成物 1

HCID 67320524Benzyl (R)-3-(2-benzyloxycarbonylaminoethylsulfanyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)ureido]propionate収率 29.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

A solution of 166 mg (1.02 mmol) of 1,1′-carbonyldiimidazole in 8 ml of DMF was mixed with 515 mg (1.02 mmol) of the trifluoroacetate from step B and 0.57 ml (415 mg, 4.10 mmol) of triethylamine. A solution of 328 mg (1.02 mmol) of (9S,12R)-12-amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-one (1-1E) in 8 ml of DMF was added to this mixture under argon, and the mixture was stirred at RT overnight. The reaction mixture was then concentrated and separated by preparative HPLC. The required fractions were combined and freed of acetonitrile. The resulting aqueous solution was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate, filtered and concentrated. 222 mg of the title compound were obtained.

後処理

  1. concentrationThe reaction mixture was then concentrated
  2. customseparated by preparative HPLC
  3. extractionThe resulting aqueous solution was extracted with ethyl acetate
  4. dry with materialthe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-4cc18421303540ec8d21be5d383db529
出典データセット
uspto-grants-2013_11
特許番号
US08580777B2

反応ノート

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