(S)-4-[[(S)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-5-methoxy-pentanoic acid tert-butyl ester → (S)-4-[(S)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-2-oxo-piperazin-1-yl]-5-methoxy-pentanoic acid

HRID 2095530Notes

Reaction equation

C([O:5][C:6](=[O:36])[CH2:7][CH2:8][C@H:9]([N:13]([C:20](=[O:35])[C@@H:21]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[C:26]([Cl:34])[CH:25]=1)[CH3:22])[CH2:14][CH:15](OC)OC)[CH2:10][O:11][CH3:12])(C)(C)C.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>>[Cl:34][C:26]1[CH:25]=[C:24]([N:23]2[CH2:15][CH2:14][N:13]([C@H:9]([CH2:10][O:11][CH3:12])[CH2:8][CH2:7][C:6]([OH:5])=[O:36])[C:20](=[O:35])[C@@H:21]2[CH3:22])[CH:29]=[CH:28][C:27]=1[C:30]([F:31])([F:32])[F:33]

Participants

Reactant 2

HCID 67074277(S)-4-[[(S)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-5-methoxy-pentanoic acid tert-butyl ester

HCID 131722655TFA triethylsilane

Product 1

HCID 67074561(S)-4-[(S)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-2-oxo-piperazin-1-yl]-5-methoxy-pentanoic acidYield 36%

Procedure

In analogy to intermediate 44C, (S)-4-[[(S)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-5-methoxy-pentanoic acid tert-butyl ester was cyclized with trifluoroacetic acid/triethylsilane to give the titled compound in 36% yield as brown oil. MS: 421.2 (MH+, 1Cl).

Sources & evidence

ORD record: ord-1a09739ad3ea46c7a8d1a261344741ce
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445674B2

Reaction notes

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