Sodium Bicarbonate → [3-((R)-5-Amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-(3-bromo-[1,7]naphthyridin-8-yl)-amine

HRID 925460Notes

Reaction equation

HRID 925460 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]([NH2:23])[CH:20]=[CH:19][C:18]=2[F:24])([CH:14]([F:16])[F:15])[N:13]=1)(C)(C)C.[Br:26][C:27]1[CH:28]=[N:29][C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[N:32][C:31]=2Cl.C([O-])(O)=O.[Na+]>C(O)(C)(C)C.Cl.O1CCOCC1>[NH2:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:17]2[CH:22]=[C:21]([NH:23][C:31]3[N:32]=[CH:33][CH:34]=[C:35]4[C:30]=3[N:29]=[CH:28][C:27]([Br:26])=[CH:36]4)[CH:20]=[CH:19][C:18]=2[F:24])([CH:14]([F:15])[F:16])[N:13]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 66666080[(R)-5-(5-Amino-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl esterHCID 722135923-Bromo-8-chloro-1,7-naphthyridine

Product 1

HCID 71549953[3-((R)-5-Amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-(3-bromo-[1,7]naphthyridin-8-yl)-amine

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

[(R)-5-(5-Amino-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]carbamic acid tert-butyl ester (CAS registry 1262859-09-5) (250 mg, 0.696 mmol) and 3-bromo-8-chloro-[1,7]naphthyridine [Heteroaryl 1] (186 mg, 0.765 mmol) were dissolved in tert-Butanol (4 ml) in a microwave vial and HCl (0.174 ml of a 4M solution in dioxane) was added. The vial was sealed and heated to 100° C. for 1 h. The reaction mixture was cooled to rt and added to a saturated NaHCO3 solution (20 ml) and stirred at rt for 10 min.

Workup

  1. additionwas added
  2. customThe vial was sealed
  3. temperatureThe reaction mixture was cooled to rt

Sources & evidence

ORD record
ord-43829f67077540bcaf0b7c1bb4d07895
Source dataset
uspto-grants-2016_03
Patent number
US09284284B2

Reaction notes

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