{(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 → (2S,3S)-2-{(R)-2-amino-2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

HRID 32822Notes

Reaction equation

HRID 32822 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[CH:35][CH:34]=1)[C:9](=[O:32])[NH:10][C@H:11]([C:20](=[O:31])[NH:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[O:30])[CH2:28][CH3:29])[N:26]=1)[C@H:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[NH2:7][C@H:8]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[CH:35][CH:34]=1)[C:9]([NH:10][C@@H:11]([C@H:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])[C:20]([NH:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[O:30])[CH2:28][CH3:29])[N:26]=1)=[O:31])=[O:32]

Participants

4

Reactant 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

Product 1

HCID 86603387(2S,3S)-2-{(R)-2-amino-2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

{(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 (0.19 mmol) was dissolved in a 30% v/v solution of trifluoroacetic acid in dichloromethane (5 mL) at 0° C. After stirring for 2 hours the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous layer was adjusted to pH=8 by the addition of solid sodium bicarbonate. The aqueous layer was again extracted with ethyl acetate (2×). The combined organic layers was dried over sodium sulfate, filtered and concentrated in vacuo to give crude (2S,3S)-2-{(R)-2-amino-2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide which was used immediately and without further purification.

Workup

  1. customwas partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  2. additionThe aqueous layer was adjusted to pH=8 by the addition of solid sodium bicarbonate
  3. extractionThe aqueous layer was again extracted with ethyl acetate (2×)
  4. dry with materialThe combined organic layers was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee93d14a79024912aaef415ffd4d6601
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Reaction notes

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