Tetrahydrofuran → (2S,4R)-1-(1-carbamoyl-1H-indol-3-ylcarbamoyl)-4-fluoro-pyrrolidine-2-carboxylic acid benzyl ester

HRID 1527377Notes

Reaction equation

HRID 1527377 reaction equation
OC(C(F)(F)F)=O.[CH2:8]([O:15][C:16]([C@@H:18]1[CH2:22][C@@H:21]([F:23])[CH2:20][NH:19]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[N:24]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]([C:36]([NH2:38])=[O:37])[CH:28]=1)=[C:25]=[O:26].C1COCC1.C(N(CC)CC)C>O>[CH2:8]([O:15][C:16]([C@@H:18]1[CH2:22][C@@H:21]([F:23])[CH2:20][N:19]1[C:25](=[O:26])[NH:24][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]([C:36](=[O:37])[NH2:38])[CH:28]=1)=[O:17])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 575200853-Isocyanato-indole-1-carboxylic acid amideHCID 131733200(2S,4R)-4-fluoro-pyrrolidine-2-carboxylic acid benzyl ester TFA salt

Product 1

HCID 68283894(2S,4R)-1-(1-carbamoyl-1H-indol-3-ylcarbamoyl)-4-fluoro-pyrrolidine-2-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (2S,4R)-4-fluoro-pyrrolidine-2-carboxylic acid benzyl ester TFA salt (4.45 g, 13.2 mmol), 3-isocyanato-indole-1-carboxylic acid amide (2.65 g, 13.2 mmol) (prepared as described in Scheme A1) and THF (66 mL) was added triethylamine (5.51 mL, 39.6 mmol). The resulting solution was stirred at RT under nitrogen for 1 h until completion of the reaction. The mixture was poured in water and extracted with EtOAc. The organic layer was washed with an aqueous saturated solution of NaHCO3, dried over Na2SO4, filtered and concentrated. The crude material was purified by flash column chromatography on silica gel (c-hexane/EtOAc 9:1 to pure EtOAc) to give the desired compound. TLC, Rf (CH2Cl2/MeOH 9:1)=0.40; MS: 425.2 [M+H]+; tR (HPLC conditions a): 3.6 min.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with an aqueous saturated solution of NaHCO3
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash column chromatography on silica gel (c-hexane/EtOAc 9:1 to pure EtOAc)

Sources & evidence

ORD record
ord-2501bf94a0854a1d849c33a6cdf8d32e
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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