4-Methylmorpholine → N-(3-ethynyl-5-fluoro-4-methanesulfonylaminobenzyl)-3-(2-methyl-6-trifluoromethylpyridin-3-yl)acrylamide

HRID 2265990Notes

Reaction equation

HRID 2265990 reaction equation
Cl.[C:2]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([F:17])[C:11]=1[NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH2:7][NH2:8])#[CH:3].CN1CCOCC1.[CH3:25][C:26]1[C:31]([CH:32]=[CH:33][C:34](O)=[O:35])=[CH:30][CH:29]=[C:28]([C:37]([F:40])([F:39])[F:38])[N:27]=1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1>[C:2]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([F:17])[C:11]=1[NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH2:7][NH:8][C:34](=[O:35])[CH:33]=[CH:32][C:31]1[C:26]([CH3:25])=[N:27][C:28]([C:37]([F:38])([F:39])[F:40])=[CH:29][CH:30]=1)#[CH:3]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 685099343-(2-Methyl-6-trifluoromethylpyridin-3-yl)acrylic acidHCID 866255193-Ethynyl-5-fluoro-4-methansulfonylaminobenzylamine hydrochloride

Product 1

HCID 74382538N-(3-ethynyl-5-fluoro-4-methanesulfonylaminobenzyl)-3-(2-methyl-6-trifluoromethylpyridin-3-yl)acrylamideYield 75.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-ethynyl-5-fluoro-4-methansulfonylaminobenzylamine hydrochloride (73 mg, 0.26 mmol) in THF (5 mL) was added N-methylmorpholine (43 μL, 0.39 mmol). After stirring for 5 minutes, 3-(2-methyl-6-trifluoromethylpyridin-3-yl)acrylic acid (60 mg, 0.26 mmol) and 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM, 73 mg, 0.26 mmol) were added. The mixture was stirred at room temperature overnight, concentrated under reduced pressure, and diluted with EtOAc and water. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by recrystallization from EtOAc/hexane to give N-(3-ethynyl-5-fluoro-4-methanesulfonylaminobenzyl)-3-(2-methyl-6-trifluoromethylpyridin-3-yl)acrylamide (89 mg, 75.5%) as solid.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with EtOAc and water
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by recrystallization from EtOAc/hexane

Sources & evidence

ORD record
ord-fc49b95dfcad4a6eaafc40c1ad7dcfe8
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

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