Hydrochloric Acid → HCID 68283562, compound

HRID 1527579Notes

Reaction equation

HRID 1527579 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][C:15]([N:17]1[C@H:22]([C:23](=[O:34])[NH:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=3[F:33])[CH2:21][C@@H:20]3[C@H:18]1[CH2:19]3)=[O:16])[CH:9]=[C:8]2[C:35](=[O:37])[CH3:36])=[O:4].[Li+].[OH-].Cl>C1COCC1.O>[C:35]([C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=2)[N:10]([CH2:14][C:15]([N:17]2[C@H:22]([C:23](=[O:34])[NH:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=3[F:33])[CH2:21][C@@H:20]3[C@H:18]2[CH2:19]3)=[O:16])[CH:9]=1)(=[O:37])[CH3:36]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68283533HCID 68283533, compound

Product 1

HCID 68283562HCID 68283562, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-acetyl-1-{2-[(1R,3S,5R)-3-(3-chloro-2-fluoro-benzylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-2-yl]-2-oxo-ethyl}-1H-indole-5-carboxylic acid methyl ester (141 mg, 0.268 mmol) in THF (3 mL) and water (0.3 mL) was added 2N LiOH (1.07 mL, 2.14 mmol). Stirring of the reaction mixture was continued at 50° C. for 60 h. After cooling to RT, a 1N HCl solution was added to adjust to pH=2-3, and the resulting aqueous suspension was extracted with CH2Cl2 (3×). The combined organics were dried (phase separator) and concentrated under reduced pressure. The residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) to afford after lyophilization of the purified fractions the title compound as a white solid. MS (LC/MS): 512 [M+H]+; tR (HPLC conditions c): 4.33 min.

Workup

  1. extractionthe resulting aqueous suspension was extracted with CH2Cl2 (3×)
  2. customThe combined organics were dried (phase separator)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-f2de007267f6417bac45d4e315f73783
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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