(5-{5-[(5-Bromo-pyridine-2-carbonyl)amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester → 5-Bromo-pyridine-2-carboxylic acid[3-(5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide

HRID 81548Notes

Reaction equation

HRID 81548 reaction equation
C(OC(=O)[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][N:27]=3)=[O:25])[CH:20]=[CH:19][C:18]=2[F:33])([CH:14]([F:16])[F:15])[N:13]=1)(C)(C)C>Cl.O1CCOCC1.CO>[NH2:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][N:27]=3)=[O:25])[CH:20]=[CH:19][C:18]=2[F:33])([CH:14]([F:15])[F:16])[N:13]=1

Participants

5

Reactant 1

HCID 66665653(5-{5-[(5-Bromo-pyridine-2-carbonyl)amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

Product 1

HCID 509145465-Bromo-pyridine-2-carboxylic acid[3-(5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 100 mg (0.184 mmol) (5-{5-[(5-bromo-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester in 1.4 ml 4N HCl in dioxane was stirred at 50° C. After 15 min 0.3 ml 3N HCl in MeOH were added and the now homogeneous solution was stirred for 3 h. The mixture was concentrated and crystallized from EtOH/TBME to yield the title compound.

Workup

  1. concentrationThe mixture was concentrated
  2. customcrystallized from EtOH/TBME

Sources & evidence

ORD record
ord-6b9f647a996c44a7bf220d535bf87bad
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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