Sodium Carbonate → HCID 71112763, compound

HRID 876381Notes

Reaction equation

HRID 876381 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[NH2:31][C:32]1[CH:33]=[CH:34][C:35]([F:48])=[C:36]([C@:38]2([CH:45]([F:47])[F:46])[CH2:43][CH2:42][O:41][C:40]([NH2:44])=[N:39]2)[CH:37]=1.C([O-])([O-])=O.[Na+].[Na+]>CO>[NH2:44][C:40]1[O:41][CH2:42][CH2:43][C@:38]([C:36]2[CH:37]=[C:32]([NH:31][C:9](=[O:11])[C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=3)[CH:33]=[CH:34][C:35]=2[F:48])([CH:45]([F:46])[F:47])[N:39]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 86712808HCID 86712808, compound

Product 1

HCID 71112763HCID 71112763, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
23 °C

Procedure

To a solution of commercially available 5-cyanopicolinic acid (55.5 mg, 375 μmol) in methanol (5 ml) was added at 0° C. 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (129 mg, 437 μmol) and the colourless solution was stirred at 0° C. for 30 min. Then a solution of (S)-4-(5-amino-2-fluorophenyl)-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate E9.1) (81 mg, 312 μmol) in methanol (5 ml) was added dropwise at 0° C. via syringe. The reaction mixture was stirred at 23° C. for 16 h. Poured into 1 M Na2CO3-sol., extracted with dichloromethane, washed the organic layer with brine and dried over Na2SO4. Removal of the solvent in vacuum left a light brown oil which was chromatographed on 20 g silica gel with dichloromethane/methanol 0-10% to give (S)—N-(3-(2-amino-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide (89 mg, 229 μmol, 73.2% yield) as a white solid. MS (ISP): m/z=390.0 [M+H]+.

Workup

  1. extraction, extracted with dichloromethane
  2. washwashed the organic layer with brine
  3. dry with materialdried over Na2SO4
  4. customRemoval of the solvent in vacuum
  5. waitleft a light brown oil which
  6. customwas chromatographed on 20 g silica gel with dichloromethane/methanol 0-10%

Sources & evidence

ORD record
ord-0701c8aa5dcf4d2db22240c291cb47ec
Source dataset
uspto-grants-2015_03
Patent number
US08987255B2

Reaction notes

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