Diethyl Ether → HCID 68283675, compound

HRID 1527549Notes

Reaction equation

HRID 1527549 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:9][C@@H:8]([C:10](=[O:22])[NH:11][CH2:12][C:13]2[C:18]([F:19])=[CH:17][CH:16]=[C:15]([Cl:20])[C:14]=2[F:21])[N:7]([C:23](=[O:37])[NH:24][C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([C:34](=[O:36])[NH2:35])[CH:26]=2)[CH2:6]1)=[O:4].CCOCC.C[Si](C)(C)[O-].[K+]>C1COCC1.CCOC(C)=O.O>[C:34]([N:27]1[C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:25]([NH:24][C:23]([N:7]2[C@H:8]([C:10](=[O:22])[NH:11][CH2:12][C:13]3[C:18]([F:19])=[CH:17][CH:16]=[C:15]([Cl:20])[C:14]=3[F:21])[CH2:9][C@H:5]([C:3]([OH:4])=[O:2])[CH2:6]2)=[O:37])=[CH:26]1)(=[O:36])[NH2:35]

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 23668039Potassium trimethylsilanolateHCID 57520957HCID 57520957, compound

Product 1

HCID 68283675HCID 68283675, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S,5S)-1-(1-carbamoyl-1H-indol-3-ylcarbamoyl)-5-(3-chloro-2,6-difluoro-benzylcarbamoyl)-pyrrolidine-3-carboxylic acid methyl ester Example 353 (50 mg, 0.094 mmol) in THF (0.3 mL)/Et2O (3 mL)/H2O (0.3 mL) was added potassium trimethylsilanolate (19.5 mg, 0.2 mmol) and the resulting suspension was stirred at RT for 1.30 h. The reaction was diluted with EtOAc (15 mL) and H2O (3 mL), and the biphasic mixture was vigorously stirred for 5 min. The layers were separated, and the aqueous one was extracted with EtOAc (×2). The aqueous layer was acidified by addition of 1N HCl and extracted with EtOAc, the combined organic layers were dried over Na2SO4, filtered and concentrated. The crude material was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 25 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min) to give, after lyophilization of the purified fractions the title compound as a white solid. MS (LC-MS): 518.4 [M−H]−, 520.1 [M+H]+, 1039.3 [2M+H]+; tR (HPLC conditions f): 1.70 min.

Workup

  1. stirringthe biphasic mixture was vigorously stirred for 5 min
  2. customThe layers were separated
  3. extractionthe aqueous one was extracted with EtOAc (×2)
  4. additionThe aqueous layer was acidified by addition of 1N HCl
  5. extractionextracted with EtOAc
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 25 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min)
  10. customto give

Sources & evidence

ORD record
ord-8257fb559bb2480aa05e00fcc6a0adf0
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…