Sodium Hydroxide → HCID 68284110, compound

HRID 1527550Notes

Reaction equation

HRID 1527550 reaction equation
C[O:2][C:3](=[O:39])[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:15](=[O:17])[NH2:16])[CH:10]=[C:9]2[NH:18][C:19]([N:21]1[C@H:26]([C:27](=[O:38])[NH:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=2[F:37])[CH2:25][C@@H:24]2[C@H:22]1[CH2:23]2)=[O:20].[OH-].[Na+]>C1COCC1.O>[C:15]([N:11]1[C:12]2[C:8](=[CH:7][C:6]([O:5][CH2:4][C:3]([OH:39])=[O:2])=[CH:14][CH:13]=2)[C:9]([NH:18][C:19]([N:21]2[C@H:26]([C:27](=[O:38])[NH:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=3[F:37])[CH2:25][C@@H:24]3[C@H:22]2[CH2:23]3)=[O:20])=[CH:10]1)(=[O:17])[NH2:16]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68283474HCID 68283474, compound

Product 1

HCID 68284110HCID 68284110, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1-carbamoyl-3-{[(1R,3S,5R)-3-(3-chloro-2-fluoro-benzylcarbamoyl)-2-aza-bicyclo[3.1.0]hexane-2-carbonyl]-amino}-1H-indol-5-yloxy)-acetic acid methyl ester Example 133 (85 mg, 0.145 mmol) in THF (1.2 mL) and H2O (120 μL) was added NaOH 1N (290 μL, 0.29 mmol) and the reaction mixture was stirred at RT for 20 min. The crude was directly purified using trimethylaminopropyl cartridge (Mega Bond Elut-SAX, 1 g from Varian) pre-washed with CH3CN (10 mL) and the compound was released with 10 mL of HCl 0.1N in CH3CN. The resulting solution was concentrated and purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 15 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min) to give the desired material after lyophilization of the purified fractions. MS (UPLC-MS): 544.3/546.3 [M+H]+, 566.4/568.3 [M+Na]+, 542.3/544.4 [M−H]−; tR (HPLC conditions f): 1.72 min.

Workup

  1. customThe crude was directly purified
  2. washpre-washed with CH3CN (10 mL)
  3. concentrationThe resulting solution was concentrated
  4. custompurified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 15 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min)

Sources & evidence

ORD record
ord-45c0b1ee06fe44f897cfd0fe4921cb37
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…