1,2-Dichloroethane → HCID 86689161, compound

HRID 1752477Notes

Reaction equation

HRID 1752477 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[O:9][CH2:10][C:11]([F:24])([F:23])[C@:12]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17]([NH2:22])[N:16]=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[C:28]([C:37](O)=[O:38])=[N:29][CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O.CC(OC)(C)C>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[O:9][CH2:10][C:11]([F:23])([F:24])[C@:12]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17]([NH:22][C:37]([C:28]3[C:27]([Cl:26])=[CH:32][C:31]([C:33]([F:35])([F:34])[F:36])=[CH:30][N:29]=3)=[O:38])[N:16]=2)([CH3:14])[N:13]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 28219083-Chloro-5-(trifluoromethyl)pyridine-2-carboxylic acidHCID 71271579HCID 71271579, compound

Product 1

HCID 86689161HCID 86689161, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of [(R)-4-(6-amino-3-fluoro-pyridin-2-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-carbamic acid tert-butyl ester (134 mg, 0.372 mmol) in DMF (1.3 ml) was added 3-chloro-5-trifluoromethyl-pyridine-2-carboxylic acid (101 mg, 0.446 mmol) and HOAt (91 mg, 0.669 mmol). The mixture was cooled to 0° C., EDC*HCl (107 mg, 0.558) was added and the mixture stirred for 1 h while allowing to warm to rt. To the reaction mixture was added TBME and water, the layers were separated and the aq. layer extracted with TBME. The combined organic layers were washed with sat. aq. NaHCO3, sat. aq. NaCl, dried with MgSO4 and evaporated. The residue was purified by chromatography on silica gel (cyclohexane/EtOAc 6:1 to 5:1) to provide the title compound as colorless solid.

Workup

  1. temperatureto warm to rt
  2. customthe layers were separated
  3. extractionthe aq. layer extracted with TBME
  4. washThe combined organic layers were washed with sat. aq. NaHCO3, sat. aq. NaCl
  5. dry with materialdried with MgSO4
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel (cyclohexane/EtOAc 6:1 to 5:1)

Sources & evidence

ORD record
ord-6a72c391243e4678912170c7947ca9a3
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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