Propargylamine → HCID 56960296, compound

HRID 409337Notes

Reaction equation

HRID 409337 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.[CH2:17]([NH2:20])[C:18]#[CH:19]>C(#N)C>[F:14][C:13]([F:16])([F:15])[O:12][C:10]1[CH:9]=[CH:8][C:6]2[N:7]=[C:3]([CH2:2][NH:20][CH2:17][C:18]#[CH:19])[S:4][C:5]=2[CH:11]=1

Participants

4

Reactant 2

HCID 239041PropargylamineHCID 68277893HCID 68277893, compound

Product 1

HCID 56960296HCID 56960296, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-(bromomethyl)-6-(trifluoromethoxy)benzo[d]thiazole (3.8 g, 0.0122 mol) and propargylamine (1.7 g, 2.5 eq) were dissolved in acetonitrile (50 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, 0.5 ml of NH4OH was add (pH=9-10) and the organic phase was separated, dried over Na2SO4, evaporated and the residue purified by chromatography (hexane-EtOAc) to give 3 g (86%) of N-((6-(trifluoromethoxy)benzo[d]thiazol-2-yl)methyl)prop-2-yn-1-amine. The free base was dissolved in 100 ml Et2O and HCl/IPA was added. The white suspension that was obtained was filtered and dried to give 2.7 g (mp=188-189° C., dec) of white solid, which was identified as the HCl salt of Compound B. 1H-NMR (of the HCl salt of the title compound, DMSOd6) δ 10.23 (br s, 2H, NH2), 8.35 (s, 1H, Ar), 8.16 (d, 1H, Ar), 7.57 (d, 1H, Ar), 4.76 (s, 2H, C—CH2) 4.04 (d, 2H, N—CH2—C), 3.74 (s, 1H, CH); 13C-NMR (DMSOd6) δ 164.40, 150.66, 145.74, 136.53, 124.01, 120.39, 120.10, 115.54, 79.84, 74.88, 46.05, 35.80; LCMS (ES-API for free base) 287.0 (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, 0.5 ml of NH4OH
  6. additionwas add (pH=9-10)
  7. customthe organic phase was separated
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customthe residue purified by chromatography (hexane-EtOAc)

Sources & evidence

ORD record
ord-bad0fa6decfc4b9e891210c4bff2ff5b
Source dataset
uspto-grants-2014_06
Patent number
US08759382B2

Reaction notes

Loading…