Hydrochloric Acid → [3-((3R,6R)-5-Amino-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-(7-chloro-pyrido[3,2-d]pyrimidin-4-yl)-amine di-hydrochloride

HRID 925462Notes

Reaction equation

HRID 925462 reaction equation
C(OC(=O)[NH:7][C:8]1[C@:9]([CH3:27])([C:23]([F:26])([F:25])[F:24])[O:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:16]=2[F:22])([CH3:14])[N:13]=1)(C)(C)C.[Cl:29][C:30]1[C:31]2[N:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:32]=2[N:33]=[CH:34][N:35]=1.[ClH:41].C([O-])(O)=O.[Na+]>CC(O)(C)C.O1CCOCC1>[ClH:29].[ClH:41].[NH2:7][C:8]1[C@:9]([CH3:27])([C:23]([F:24])([F:25])[F:26])[O:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([NH:21][C:30]3[C:31]4[N:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:32]=4[N:33]=[CH:34][N:35]=3)[CH:18]=[CH:17][C:16]=2[F:22])([CH3:14])[N:13]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 66666212[(2R,5R)-5-(5-Amino-2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl esterHCID 714284454,7-Dichloropyrido[3,2-d]pyrimidine

Product 1

HCID 71550948[3-((3R,6R)-5-Amino-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-(7-chloro-pyrido[3,2-d]pyrimidin-4-yl)-amine di-hydrochloride

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [(2R,5R)-5-(5-amino-2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (CAS registry 1262859-70-0) (138 mg, 0.34 mmol) and 4,7-dichloro-pyrido[3,2-d]pyrimidine (CAS registry 917757-12-1) (75 mg, 0.374 mmol) in tBuOH (2 ml) was added 0.1 ml 4N HCl in dioxane and the reaction mixture was heated in a microwave oven for 1 h at 100° C. The reaction mixture was basified with saturated NaHCO3 solution and the product was extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was dissolved in THF, acidified with 1N HCl in Et2O, and concentrated. The remaining yellow solid was two times triturated with Et2O and subsequently dried to afford the title compound as light yellow amorphous solid.

Workup

  1. extractionthe product was extracted with EtOAc
  2. washCombined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in THF
  7. concentrationconcentrated
  8. customtriturated with Et2O
  9. customsubsequently dried

Sources & evidence

ORD record
ord-32699ed361a3467684f8903a50c01193
Source dataset
uspto-grants-2016_03
Patent number
US09284284B2

Reaction notes

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