4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 86732229, compound

HRID 930396Notes

Reaction equation

HRID 930396 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].[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[NH2:30][C:31]1[CH:32]=[C:33]([F:51])[C:34]([F:50])=[C:35]([C@:37]2([CH2:48][F:49])[CH2:42][C@@H:41]([C:43]([F:46])([F:45])[F:44])[O:40][C:39]([NH2:47])=[N:38]2)[CH:36]=1>CO>[NH2:47][C:39]1[O:40][C@H:41]([C:43]([F:44])([F:46])[F:45])[CH2:42][C@:37]([C:35]2[CH:36]=[C:31]([NH:30][C:9](=[O:11])[C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=3)[CH:32]=[C:33]([F:51])[C:34]=2[F:50])([CH2:48][F:49])[N:38]=1

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 86732228HCID 86732228, compound

Product 1

HCID 86732229HCID 86732229, compoundYield 36.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a cooled (ice bath) solution of 5-cyanopicolinic acid (0.043 g, 0.293 mmol) in MeOH (10.0 mL) was added 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (0.094 g, 0.318 mmol). After stirred for 30 min, (4S,6S)-4-(5-amino-2,3-difluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.080 g, 0.244 mmol) in MeOH (10.0 mL) was added dropwise. The reaction was then stirred at room temperature for 17 h. LCMS showed about 30% remaining starting material. The reaction was quenched with saturated sodium bicarbonate solution. MeOH was removed by rotary evaporation. The aqueous residue was extracted with EtOAc (2×). The organic extracts were combined, concentrated and purified by Shimadzu HPLC to afford N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-cyanopicolinamide (0.041 g, 0.090 mmol, 36.7% yield) as white solid. MS m/z=458.1 [M+H]+. Calculated for C19H13F6N5O2: 457.3

Workup

  1. stirringThe reaction was then stirred at room temperature for 17 h
  2. customThe reaction was quenched with saturated sodium bicarbonate solution
  3. customMeOH was removed by rotary evaporation
  4. extractionThe aqueous residue was extracted with EtOAc (2×)
  5. concentrationconcentrated
  6. custompurified by Shimadzu HPLC

Sources & evidence

ORD record
ord-440e741139574d00902d62e569014bac
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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