Triethylamine → [(1R,3S,5R)-2-(1-Carbamoyl-1H-indol-3-ylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-carbamic acid 3-chloro-2-fluoro-phenyl ester

HRID 1527535Notes

Reaction equation

HRID 1527535 reaction equation
[Cl:1][C:2]1[C:3]([F:19])=[C:4]([O:8][C:9](=[O:18])[NH:10][CH2:11][C@@H:12]2[CH2:17][C@@H:16]3[C@@H:14]([CH2:15]3)[NH:13]2)[CH:5]=[CH:6][CH:7]=1.FC(F)(F)C([O-])=O.CCN(CC)CC.[N:34]([C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:39]([C:46]([NH2:48])=[O:47])[CH:38]=1)=[C:35]=[O:36]>C1COCC1>[Cl:1][C:2]1[C:3]([F:19])=[C:4]([O:8][C:9](=[O:18])[NH:10][CH2:11][C@@H:12]2[CH2:17][C@@H:16]3[C@@H:14]([CH2:15]3)[N:13]2[C:35](=[O:36])[NH:34][C:37]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([C:46](=[O:47])[NH2:48])[CH:38]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 84468TrifluoroacetateHCID 575200853-Isocyanato-indole-1-carboxylic acid amideHCID 68283842[(1R,3S,5R)-1-(2-aza-bicyclo[3.1.0]hex-3-yl)methyl]-carbamic acid 3-chloro-2-fluoro-phenyl ester

Product 1

HCID 68283648[(1R,3S,5R)-2-(1-Carbamoyl-1H-indol-3-ylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-carbamic acid 3-chloro-2-fluoro-phenyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [(1R,3S,5R)-1-(2-aza-bicyclo[3.1.0]hex-3-yl)methyl]-carbamic acid 3-chloro-2-fluoro-phenyl ester, trifluoroacetate (60.0 mg, 0.211 mmol) and Et3N (88 μl, 0.62 mmol) in THF (5 mL) was added 3-isocyanato-indole-1-carboxylic acid amide (43.0 mg, 0.211 mmol; prepared as described in Scheme A1). The solution was stirred at RT under a nitrogen atmosphere for 3 days. Purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) afforded after lyophilization of the purified HPLC fractions the title compound. MS (LC/MS): 486.0 [M+H]+; tR (HPLC conditions k): 3.57 min.

Workup

  1. customPurified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min)

Sources & evidence

ORD record
ord-c4da7691e0984d5c90ab8352315346a7
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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