Sodium hydride → HCID 68284846, compound

HRID 1527608Notes

Reaction equation

HRID 1527608 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([O:10][C:11]([F:14])([F:13])[F:12])=[CH:8][CH:7]=[CH:6][C:5]=1[NH:15][C:16]([CH:18]1[CH2:23][CH:22]2[CH:20]([CH2:21]2)[N:19]1[C:24](=[O:39])[CH2:25][N:26]1[C:34]2[C:29](=[CH:30][C:31]([OH:35])=[CH:32][CH:33]=2)[C:28]([C:36](=[O:38])[CH3:37])=[N:27]1)=[O:17].Br[CH2:41][CH2:42][O:43][CH3:44]>CN(C=O)C>[F:3][C:4]1[C:9]([O:10][C:11]([F:14])([F:13])[F:12])=[CH:8][CH:7]=[CH:6][C:5]=1[NH:15][C:16]([C@@H:18]1[CH2:23][C@@H:22]2[C@@H:20]([CH2:21]2)[N:19]1[C:24](=[O:39])[CH2:25][N:26]1[C:34]2[C:29](=[CH:30][C:31]([O:35][CH2:41][CH2:42][O:43][CH3:44])=[CH:32][CH:33]=2)[C:28]([C:36](=[O:38])[CH3:37])=[N:27]1)=[O:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 77462383HCID 77462383, compound

Product 1

HCID 68284846HCID 68284846, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (60% in Mineral oil, 4.8 mg, 0.121 mmol) in DMF (5 mL) at 0° C. was added 1R,3S,5R)-2-[2-(3-acetyl-5-hydroxy-indazol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid (2-fluoro-3-trifluoromethoxy-phenyl)-amide (60 mg, 0.115 mmol). After stirring for 5 min, 1-bromo-2-methoxyethane (0.016 mL, 0.173 mmol) was added and the reaction mixture was stirred at RT for 16 h. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. The crude residue was purified by preparative HPLC (Waters Sunfire C18-ODB, 5 um, 30×100 mm, flow: 40 mL/min, gradient: 0-18.5 min 5% to 100% CH3CN, 18.5-20 min 100% CH3CN, H2O and CH3CN containing 0.1% TFA). Further purification by flash chromatography on silica gel (c-hexane/EtOAc 1:0 to 0:1) afforded the title compound. MS (UPLC-MS): 579.3. tR (HPLC conditions f): 2.07 min.

Workup

  1. stirringthe reaction mixture was stirred at RT for 16 h
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by preparative HPLC (Waters Sunfire C18-ODB, 5 um, 30×100 mm, flow: 40 mL/min, gradient: 0-18.5 min 5% to 100% CH3CN, 18.5-20 min 100% CH3CN, H2O and CH3CN containing 0.1% TFA)
  8. customFurther purification by flash chromatography on silica gel (c-hexane/EtOAc 1:0 to 0:1)

Sources & evidence

ORD record
ord-33614ecc5a7c4f94830ca769a2929818
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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