Tert-butyl 5-(5-(5-chloropicolinamido)-2-fluorophenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-ylcarbamate → N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-5-chloropicolinamide

HRID 2196336Notes

Reaction equation

HRID 2196336 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([F:35])=[C:15]([C:17]3([CH3:34])[C:23]([F:25])([F:24])[CH2:22][O:21][CH2:20][C:19]([NH:26]C(=O)OC(C)(C)C)=[N:18]3)[CH:16]=2)=[O:9])=[N:6][CH:7]=1>O1CCOCC1.Cl>[NH2:26][C:19]1[CH2:20][O:21][CH2:22][C:23]([F:24])([F:25])[C:17]([C:15]2[CH:16]=[C:11]([NH:10][C:8](=[O:9])[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=3)[CH:12]=[CH:13][C:14]=2[F:35])([CH3:34])[N:18]=1

Participants

4

Reactant 1

HCID 66666053Tert-butyl 5-(5-(5-chloropicolinamido)-2-fluorophenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-ylcarbamate

Product 1

HCID 50913364N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-5-chloropicolinamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 5-(5-(5-chloropicolinamido)-2-fluorophenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-ylcarbamate (0.210 g, 0.41 mmol) in 10% dioxane in HCl was heated in a sealed tube at 55° C. for 5 h. Reaction mixture was concentrated under reduced pressure, basified with 2% methanolic ammonia and purified by column chromatography on silica gel with MeOH/DCM (3:97) to obtain the title compound as an off white solid. Yield=0.08 g (50%). TLC (20% methanol in chloroform): Rf=0.35, m.p.=190-193° C.,

Workup

  1. customReaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. custompurified by column chromatography on silica gel with MeOH/DCM (3:97)

Sources & evidence

ORD record
ord-7693b1615997468092a04b459f6a2e74
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Reaction notes

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