1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → {(R)-[4-(2-Morpholin-4-yl-ethoxy)-phenyl]-[(1S,2S)-2-phenyl-1-(4-propionyl-thiazol-2-ylcarbamoyl)-propylcarbamoyl]-methyl}-carbamic acid-tert-butyl ester

HRID 32821ノート

反応式

HRID 32821 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][CH:14]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC([C@@H]2C(=O)[N:39]([C@@H:42]([C@H:55]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH3:56])[C:43]([NH:45][C:46]3[S:47][CH:48]=[C:49]([C:51](=[O:54])[CH2:52][CH3:53])[N:50]=3)=[O:44])C(=O)N2)=CC=1.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:17][CH:18]=1)[C:10](=[O:12])[NH:39][C@H:42]([C:43](=[O:44])[NH:45][C:46]1[S:47][CH:48]=[C:49]([C:51](=[O:54])[CH2:52][CH3:53])[N:50]=1)[C@H:55]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[CH3:56])([CH3:3])([CH3:2])[CH3:4]

参加物

5

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11577042(2S,3S)-2-[(R)-4-(4-Methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramideHCID 68620207(R)-tert-butoxycarbonylamino-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetic acid

生成物 1

HCID 86603386{(R)-[4-(2-Morpholin-4-yl-ethoxy)-phenyl]-[(1S,2S)-2-phenyl-1-(4-propionyl-thiazol-2-ylcarbamoyl)-propylcarbamoyl]-methyl}-carbamic acid-tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(R)-tert-butoxycarbonylamino-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetic acid (≈2.93 mmol) was dissolved in tetrahydrofuran (60 mL) and (2S,3S)-2-amino-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (500 mg, 1.58 mmol) (prepared as described in example 4) was added followed by 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (600 mg, 3.12 mmol) at 0° C. The reaction mixture was allowed to slowly warm to room temperature. After stirring for 5.5 hours the reaction mixture was partitioned between ethyl acetate and brine, the organic extract was dried over sodium sulfate and concentrated in vacuo. The resulting residue purified by chromatography over silica gel eluted first with ethyl acetate and then gradient eluted with dichloromethane containing from 0 to 10% methanol. {(R)-[4-(2-Morpholin-4-yl-ethoxy)-phenyl]-[(1S,2S)-2-phenyl-1-(4-propionyl-thiazol-2-ylcarbamoyl)-propylcarbamoyl]-methyl}-carbamic acid-tert-butyl ester was obtained as a white solid (146 mg, 14%).

後処理

  1. customwas partitioned between ethyl acetate and brine
  2. extractionthe organic extract
  3. dry with materialwas dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue purified by chromatography over silica gel
  6. washeluted first with ethyl acetate
  7. washgradient eluted with dichloromethane containing from 0 to 10% methanol

出典と根拠

ORDレコード
ord-76e6f9b745e8434ba9b0de8020255fc2
出典データセット
uspto-grants-2008_09
特許番号
US07427635B2

反応ノート

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