4-Methylmorpholine → HCID 74382384, compound

HRID 2265958Notes

Reaction equation

HRID 2265958 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[C:8]([F:10])[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([C:16]#[CH:17])[CH:5]=1.CN1CCOCC1.[CH2:25]([N:27]([CH2:43][CH3:44])[C:28]1[C:33]([CH:34]=[CH:35][C:36](O)=[O:37])=[CH:32][CH:31]=[C:30]([C:39]([F:42])([F:41])[F:40])[N:29]=1)[CH3:26].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1>[CH2:43]([N:27]([CH2:25][CH3:26])[C:28]1[C:33]([CH:34]=[CH:35][C:36]([NH:2][CH2:3][C:4]2[CH:9]=[C:8]([F:10])[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([C:16]#[CH:17])[CH:5]=2)=[O:37])=[CH:32][CH:31]=[C:30]([C:39]([F:42])([F:40])[F:41])[N:29]=1)[CH3:44]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 687822843-(2-Diethylamino-6-trifluoromethyl-pyridin-3-yl)-acrylic acidHCID 866255193-Ethynyl-5-fluoro-4-methansulfonylaminobenzylamine hydrochloride

Product 1

HCID 74382384HCID 74382384, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N-(4-aminomethyl-2-ethynyl-6-fluoro-phenyl)-methanesulfonamide HCl salt (476 mg, 1.66 mmol) in THF (5 mL) was added N-methylmorpholine (0.365 ml, 3.32 mmol). The mixture was stirred for 5 minutes, to which were added 3-(2-diethylamino-6-trifluoromethyl-pyridin-3-yl)-acrylic acid (434 mg, 1.51 mmol) and 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM, 459 mg, 1.66 mmol). The mixture was stirred overnight at room temperature and was concentrated under reduced pressure. The residue was diluted with EtOAc and water. The organic layer was washed with saturated sodium bicarbonate, 1N HCl and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by recrystallization from CH2Cl2 to give the title compound (645 mg, 83%).

Workup

  1. stirringThe mixture was stirred overnight at room temperature
  2. concentrationwas concentrated under reduced pressure
  3. additionThe residue was diluted with EtOAc and water
  4. washThe organic layer was washed with saturated sodium bicarbonate, 1N HCl and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by recrystallization from CH2Cl2

Sources & evidence

ORD record
ord-131de14a8331421d977fd6a05c13f4b8
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

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