Hydrochloric Acid → Rac-2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-(tetrahydro-2h-pyran-2-yl)pyridine-3,5-dicarbonitrile

HRID 1873603Notes

Reaction equation

HRID 1873603 reaction equation
N[C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[C:5]([C:16]#[N:17])=[C:4]([S:18][CH2:19][C:20]2[N:21]=[C:22]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[S:23][CH:24]=2)[N:3]=1.N(OCCC(C)C)=O.Cl>C1COCC1.[Cu](Cl)Cl>[Cl:31][C:28]1[CH:27]=[CH:26][C:25]([C:22]2[S:23][CH:24]=[C:20]([CH2:19][S:18][C:4]3[C:5]([C:16]#[N:17])=[C:6]([CH:10]4[CH2:15][CH2:14][CH2:13][CH2:12][O:11]4)[C:7]([C:8]#[N:9])=[CH:2][N:3]=3)[N:21]=2)=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 24959059Rac-2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-(tetrahydro-2h-pyran-2-yl)-pyridine-3,5-dicarbonitrile

Product 1

HCID 24959787Rac-2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-(tetrahydro-2h-pyran-2-yl)pyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

100 mg (0.21 mmol) of the compound from Example 14 are initially charged in 5 ml of dry THF, and 167 mg (1.42 mmol) of isopentyl nitrite and 3 mg (0.02 mmol) of copper(II) chloride are added. The reaction mixture is stirred at RT for 8 h. Another 3 mg (0.02 mmol) of copper(II)-chloride are added, and the reaction mixture is stirred at RT for another 12 h. 6 ml of 1 N hydrochloric acid are then added to the mixture. The aqueous phase is extracted twice with in each case 10 ml ethyl acetate. The combined organic phases are washed once with 5 ml of saturated aqueous sodium bicarbonate solution and once with 5 ml of saturated aqueous sodium chloride solution. The mixture is then dried over magnesium sulfate. After removal of the solvent the residue is purified by preparative HPLC (column: YMC GEL ODS-AQ S-5, 15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

  1. stirringthe reaction mixture is stirred at RT for another 12 h
  2. extractionThe aqueous phase is extracted twice with in each case 10 ml ethyl acetate
  3. washThe combined organic phases are washed once with 5 ml of saturated aqueous sodium bicarbonate solution and once with 5 ml of saturated aqueous sodium chloride solution
  4. dry with materialThe mixture is then dried over magnesium sulfate
  5. customAfter removal of the solvent the residue
  6. customis purified by preparative HPLC (column: YMC GEL ODS-AQ S-5, 15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)

Sources & evidence

ORD record
ord-8ffed24585e34145aae0af415d164605
Source dataset
uspto-grants-2012_11
Patent number
US08304412B2

Reaction notes

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