4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 86732210, compound

HRID 930381Notes

Reaction equation

HRID 930381 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]2([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([C:28](O)=[O:29])=[N:26][CH:27]=1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1.CO>[NH2:18][C:10]1[O:11][C@H:12]([C:14]([F:17])([F:15])[F:16])[CH2:13][C@:8]([C:4]2[CH:3]=[C:2]([NH:1][C:28](=[O:29])[C:25]3[CH:24]=[CH:23][C:22]([Cl:21])=[CH:27][N:26]=3)[CH:7]=[CH:6][CH:5]=2)([CH2:19][F:20])[N:9]=1

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 27628725-Chloro-2-picolinic acidHCID 86732209HCID 86732209, compound

Product 1

HCID 86732210HCID 86732210, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of (4S,6S)-4-(3-aminophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.080 g, 0.275 mmol) and 5-chloro-2-pyridinecarboxylic acid (0.048 g, 0.302 mmol) in THF/MeOH (3/1.2 mL) was stirred at room temperature and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (0.089 g, 0.302 mmol) was added. The reaction mixture was stirred for 30 min. The reaction was quenched with saturated NaHCO3 solution and extracted with dichloromethane. The combined organic layers were dried over Na2SO4, filtered, concentrated. The crude material was purified by column chromatographed on silica gel using 10-50% EtOAc/hexane to afford a white solid as N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)phenyl)-5-chloropicolinamide (0.075 g, 0.174 mmol, 63.4% yield). MS m/z=430.9 [M+H]+. Calculated for C18H15ClF4N4O2: 430.8

Workup

  1. stirringThe reaction mixture was stirred for 30 min
  2. customThe reaction was quenched with saturated NaHCO3 solution
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by column
  8. customchromatographed on silica gel using 10-50% EtOAc/hexane

Sources & evidence

ORD record
ord-5a0f03e5df58468485b8d01f2175cb59
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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