Dimethylformamide → HCID 178461851, compound

HRID 572219Notes

Reaction equation

HRID 572219 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C@@H:14]([NH:16][C:17]2[CH:22]=[N:21][CH:20]=[C:19]([Cl:23])[N:18]=2)[CH3:15])[CH:9]=1)=[O:6].ClCCOCCCl.C(=O)([O-])[O-].[K+].[K+].[CH3:44][N:45]([CH3:48])[CH:46]=O>>[Cl:23][C:19]1[N:18]=[C:17]([NH:16][C@H:14]([C:10]2[CH:9]=[C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=[C:2](/[N:1]=[CH:44]\[N:45]([CH3:48])[CH3:46])[CH:3]=3)[CH:13]=[CH:12][CH:11]=2)[CH3:15])[CH:22]=[N:21][CH:20]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8115Bis(2-chloroethyl) etherHCID 11430Potassium CarbonateHCID 59331648HCID 59331648, compound

Product 1

HCID 178461851HCID 178461851, compoundYield 16%

Conditions

Temperature
180 °C

Procedure

A mixture of (S)-3-amino-N-(3-(1-(6-chloropyrazin-2-ylamino)ethyl)phenyl)-5-(trifluoromethyl)benzamide (38 mg, 0.09 mmol), 2-chloroethyl ether (0.012 mL, 0.1 mmol) and potassium carbonate (30 mg, 0.21 mmol) in N,N-dimethyl formamide (1 mL) was heated in a microwave reactor at 180° C. for 40 minutes. After this time the mixture was allowed to cool to room temperature and was filtered through cotton wool, diluted with ethyl acetate (15 mL), washed with saturated aqueous sodium hydrogen carbonate (2×10 mL), water (2×10 mL), brine (2×10 mL), dried (Na2SO4) and concentrated under reduced pressure to give a brown oil which was purified by flash chromatography (silica, ethyl acetate/methanol) followed by passage through a column of Sephadex with methanol as eluant to give the byproduct (S,Z)—N-(3-(1-(6-chloropyrazin-2-ylamino)ethyl)phenyl)-3-((dimethylamino)methyleneamino)-5-(trifluoromethyl)benzamide (7 mg, 16%) as a yellow oil.

Workup

  1. temperatureto cool to room temperature
  2. filtrationwas filtered through cotton wool
  3. additiondiluted with ethyl acetate (15 mL)
  4. washwashed with saturated aqueous sodium hydrogen carbonate (2×10 mL), water (2×10 mL), brine (2×10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customto give a brown oil which
  8. customwas purified by flash chromatography (silica, ethyl acetate/methanol)

Sources & evidence

ORD record
ord-f0a725ec88874bc38de1a4d3c2ee708f
Source dataset
uspto-grants-2015_05
Patent number
US09029386B2

Reaction notes

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