HCID 68277893, compound → HCID 56960297, compound

HRID 409338Notes

Reaction equation

HRID 409338 reaction equation
Br[CH2:2][C:3]1[S:4][C:5]2[CH:11]=[C:10]([O:12][C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:8][C:6]=2[N:7]=1>C(#N)C>[CH3:3][N:7]([CH2:2][C:3]1[S:4][C:5]2[CH:11]=[C:10]([O:12][C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:8][C:6]=2[N:7]=1)[CH2:6][C:5]#[CH:11]

Participants

3

Reactant 1

HCID 68277893HCID 68277893, compound

Product 1

HCID 56960297HCID 56960297, compoundYield 193.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-(bromomethyl)-6-(trifluoromethoxy)benzo[d]thiazole (4.4 g, 0.0141 mol) and N-Me-propargylamine (2.4 g, 2.5 eq, 0.035 mol) were dissolved in acetonitrile (70 ml) and the reaction mixture was heated to reflux for 1 h. Then it was cooled, evaporated to dryness and the residue was partitioned between EtOAc and water (100 ml:100 ml), NH4OH was add (to give pH of 9-10) and the organic phase was separated, dried over Na2SO4, evaporated and the residue purified by chromatography (hexane-EtOAc) to give 4.1 g (97%) of N-methyl-N-((6-(trifluoromethoxy)benzo[d]thiazol-2-yl)methyl)prop-2-yn-1-amine. The free base (4.1 g) was dissolved in 100 ml Et2O and HCl/IPA (2N) was added (pH=1-2). The white suspension that was obtained was filtered and the collected solid was dried to give 2.7 g (mp=117-120° C.) which was identified to be the HCl salt of compound C. 1H-NMR (of the HCl salt of the title compound, DMSOd6) δ 8.38 (s, 1H, Ar), 8.20 (d, 1H, Ar), 7.58 (d, 1H, Ar), 4.86 (br s, 2H, C—CH2) 4.22 (br s, 2H, MeN-CH2—C), 3.88 (s, 1H, CH), 2.89 (s, 3H, NMe); 13C-NMR (DMSOd6) δ 163.38, 150.96, 145.83, 136.87, 124.36, 120.36, 120.08, 115.46, 81.22, 73.60, 53.50, 44.37; LCMS (ES-API for free base) 301.0 (M+H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 1 h
  3. temperatureThen it was cooled
  4. customevaporated to dryness
  5. customthe residue was partitioned between EtOAc and water (100 ml:100 ml), NH4OH
  6. additionwas add
  7. custom(to give pH of 9-10)
  8. customthe organic phase was separated
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. customthe residue purified by chromatography (hexane-EtOAc)

Sources & evidence

ORD record
ord-03979b437cdc426e99f18f8ee3101d5b
Source dataset
uspto-grants-2014_06
Patent number
US08759382B2

Reaction notes

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