Hydrochloric Acid → 1-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid benzyl ester

HRID 1527544Notes

Reaction equation

HRID 1527544 reaction equation
OC(C(F)(F)F)=O.[F:8][C:9]([F:26])([F:25])[O:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]([C@@H:20]2[CH2:24][CH2:23][CH2:22][NH:21]2)=[O:19])[CH:14]=[CH:15][CH:16]=1.C(N(CC)CC)C.[CH2:34]([O:41][C:42]([C:44]1[N:52]2[C:47]([CH:48]=[CH:49][CH:50]=[CH:51]2)=[C:46]([N:53]=[C:54]=[O:55])[CH:45]=1)=[O:43])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.Cl>C1COCC1>[CH2:34]([O:41][C:42]([C:44]1[N:52]2[C:47]([CH:48]=[CH:49][CH:50]=[CH:51]2)=[C:46]([NH:53][C:54]([N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[C:18](=[O:19])[NH:17][C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([O:10][C:9]([F:25])([F:8])[F:26])[CH:12]=2)=[O:55])[CH:45]=1)=[O:43])[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 866738121-Isocyanato-indolizine-3-carboxylic acid benzyl esterHCID 131733207(S)-pyrrolidine-2-carboxylic acid (3-trifluoromethoxy-phenyl)-amide TFA salt

Product 1

HCID 682844901-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-pyrrolidine-2-carboxylic acid (3-trifluoromethoxy-phenyl)-amide TFA salt (328 mg, 0.845 mmol) and triethylamine (353 μl, 2.54 mmol) in THF (10 mL) was added the crude 1-isocyanato-indolizine-3-carboxylic acid benzyl ester (247 mg, 0.845 mmol, prepared as described in Scheme A6). The resulting mixture was stirred at RT under nitrogen over the week-end then poured into HCl 1N and extracted with EtOAc (×3). The combined organic extracts were washed with an aqueous saturated solution of NaHCO3, dried (Na2SO4), filtered and concentrated. The crude mixture was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1 to c-hexane/EtOAc 3:7) to afford the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.3; MS (LC/MS): 567.3 [M+H]+ 565.2 [M−H]−; tR (HPLC conditions a): 4.16 min.

Workup

  1. extractionextracted with EtOAc (×3)
  2. washThe combined organic extracts were washed with an aqueous saturated solution of NaHCO3
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude mixture was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1 to c-hexane/EtOAc 3:7)

Sources & evidence

ORD record
ord-c11d564daf6d4010862e697c1090318b
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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