Triethylamine → (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

HRID 81547

Reaction equation

HRID 81547 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:17]2[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][C:18]=2[F:24])([CH:14]([F:16])[F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[Br:26][C:27]1[CH:28]=[CH:29][C:30]([C:33](O)=[O:34])=[N:31][CH:32]=1.C1C=NC2N(O)N=NC=2C=1.CCN(CC)CC.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:17]2[CH:22]=[C:21]([NH:23][C:33]([C:30]3[CH:29]=[CH:28][C:27]([Br:26])=[CH:32][N:31]=3)=[O:34])[CH:20]=[CH:19][C:18]=2[F:24])([CH:14]([F:16])[F:15])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 181649HOAtHCID 6085445-Bromopyridine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66665663[5-(5-Amino-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

Product 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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 325 mg (0.952 mmol) [5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester, 212 mg (1.047 mmol) 5-bromo-pyridine-2-carboxylic acid, 168 mg (1.238 mmol) HOAt and 0.34 ml (2.38 mmol) Et3N in 5 ml DCM were added 237 mg (1.24 mmol) EDC.HCl. The mixture was stirred overnight. The mixture was diluted with EtOAc and washed with water, 1N HCl, brine and 5% aqueous NaHCO3. The organic phase was dried with MgSO4.H2O, filtered and purified by chromatography on silica gel (hexane/14-18% EtOAc) to give the desired product as colorless foam.

Workup

  1. washwashed with water, 1N HCl, brine and 5% aqueous NaHCO3
  2. dry with materialThe organic phase was dried with MgSO4.H2O
  3. filtrationfiltered
  4. custompurified by chromatography on silica gel (hexane/14-18% EtOAc)

Sources & evidence

ORD record
ord-26622ebb5f944976a8e4bb635e6a0038
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Linked notes

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