p-Toluenesulfonic acid → 2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazole-6-carbonitrile

HRID 1848012Notes

Reaction equation

HRID 1848012 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([C:18]#[N:19])[CH:15]=[CH:14][C:12]=2[N:13]=1.CO[C:22](OC)([CH3:24])[CH3:23].C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[CH3:23][C:22]1([CH3:24])[N:8]([C:9]2[S:10][C:11]3[CH:17]=[C:16]([C:18]#[N:19])[CH:15]=[CH:14][C:12]=3[N:13]=2)[C@@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]2[O:1]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 64952,2-DimethoxypropaneHCID 866810342-(((1R,2R)-2-Hydroxycyclohexyl)amino)benzo[d]thiazole-6-carbonitrile

Product 1

HCID 866810332-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazole-6-carbonitrileYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred mixture of 2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazole-6-carbonitrile (1.2 g, 4.5 mmol) from Step 2 of this Example and 2,2-dimethoxypropane (4.7 g, 45 mmol) in 1,4-dioxane (30 mL) were added para-toluenesulfonic acid (89 mg, 0.5 mmol) and molecular sieves (4 Å) and the mixture was heated at reflux for 15 h. The mixture was cooled to rt, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified via silica gel flash chromatography to afford 2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazole-6-carbonitrile (700 mg, 50%) as a white solid. LCMS (ESI) m/z 314 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 15 h
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified via silica gel flash chromatography

Sources & evidence

ORD record
ord-f49c5d255849499e875ccef3997986b0
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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