Dimethylformamide → HCID 89761899, compound

HRID 528537Notes

Reaction equation

HRID 528537 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([N:25]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=3[O:40][CH3:41])[C:26]3[S:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[NH:15][CH2:14][CH2:13]1.CN(C=O)C.[H-].[Na+].[C:49](OC(=O)C)(=[O:51])[CH3:50]>O.CCOC(C)=O.[Cl-].[Na+].O>[C:49]([N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[C:18]([S:22]([N:25]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=3[O:40][CH3:41])[C:26]3[S:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])[CH:17]=2)[N:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:10])([F:9])[F:11])=[CH:7][C:2]=2[Cl:1])[CH2:13][CH2:14]1)(=[O:51])[CH3:50]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 7918Acetic Anhydride3×HCID 24758Sodium hydride2×HCID 89761773HCID 89761773, compound2×

Product 1

HCID 89761899HCID 89761899, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A vial was charged with 1-(2-chloro-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (INTERMEDIATE V, 0.045 g, 0.072 mmol) and DMF (0.719 mL). Sodium hydride (60% in mineral oil) (4.31 mg, 0.108 mmol) was added to give a dark brown solution. Acetic anhydride (0.014 mL, 0.144 mmol) was added dropwise, and the mixture lightened significantly and thickened up. After stirring for 30 minutes at room temperature, additional acetic anhydride (0.014 mL, 0.144 mmol) was added and the reaction was heated to 50° C. and stirred for one hour. Additional sodium hydride (60% in mineral oil) (4.31 mg, 0.108 mmol) and acetic anhydride (0.014 mL, 0.144 mmol) were added and the reaction was stirred at 70° C. for one hour. The mixture was diluted with water and EtOAc, then with brine to break up an emulsion. The layers were separated, and the aqueous layer was extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, and concentrated. The material was purified via silica gel chromatography (12 g column, gradient elution 0 to 100% EtOAc:Heptane) to afford 4-acetyl-1-(2-chloro-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide as a white solid. m/z (ESI) 667.7 (M+H)+.

Workup

  1. customto give a dark brown solution
  2. temperaturethe reaction was heated to 50° C.
  3. stirringstirred for one hour
  4. stirringthe reaction was stirred at 70° C. for one hour
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe material was purified via silica gel chromatography (12 g column, gradient elution 0 to 100% EtOAc:Heptane)

Sources & evidence

ORD record
ord-a35f0eccb2a24e1ea30e1decd8b8b0b2
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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