Hydrochloric Acid → HCID 71009647, compound

HRID 1527595Notes

Reaction equation

HRID 1527595 reaction equation
C[O:2][C:3]([C:5]1[N:10]=[C:9]2[N:11]([CH2:17][C:18]([N:20]3[C@H:25]([C:26](=[O:37])[NH:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=4[F:36])[CH2:24][C@@H:23]4[C@H:21]3[CH2:22]4)=[O:19])[CH:12]=[C:13]([C:14](=[O:16])[CH3:15])[C:8]2=[CH:7][CH:6]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1.O>[C:14]([C:13]1[C:8]2[C:9](=[N:10][C:5]([C:3]([OH:4])=[O:2])=[CH:6][CH:7]=2)[N:11]([CH2:17][C:18]([N:20]2[C@H:25]([C:26](=[O:37])[NH:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=3[F:36])[CH2:24][C@@H:23]3[C@H:21]2[CH2:22]3)=[O:19])[CH:12]=1)(=[O:16])[CH3:15]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68284231HCID 68284231, compound

Product 1

HCID 71009647HCID 71009647, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

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-pyrrolo[2,3-b]pyridine-6-carboxylic acid methyl ester (Example 689, 70 mg, 0.133 mmol) in THF (3 mL) and water (0.3 mL) was added a 2N aqueous LiOH solution (0.664 mL, 1.33 mmol). The reaction mixture was stirred at 25° C. for 16 h, then a 1N HCl aqueous solution was added to acidify the reaction mixture to pH=2 to 3. The resulting aqueous suspension was filtered, the solid was washed with water and then dried in vacuo. The crude solid was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20% to 100% CH3CN in H2O in 20 min, 100% CH3CN 2 min, CH3CN and H2O containing 0.1% TFA). The pure fractions were combined, CH3CN was evaporated under reduced pressure and the resulting aqueous solution was lyophilized to give the title compound as a white solid. MS: 513 [M+H]+, 535 [M+Na]+; tR (HPLC conditions k): 3.14 min.

Workup

  1. filtrationThe resulting aqueous suspension was filtered
  2. washthe solid was washed with water
  3. customdried in vacuo
  4. customThe crude solid was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20% to 100% CH3CN in H2O in 20 min, 100% CH3CN 2 min, CH3CN and H2O containing 0.1% TFA)
  5. customCH3CN was evaporated under reduced pressure

Sources & evidence

ORD record
ord-cc55a50a42f347a9aadab144c0bd919e
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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