Hydrochloric Acid → N-{5-Methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-2-[4-(trifluoromethyl) phenyl]thiazole-4-carboxamide

HRID 1748629Notes

Reaction equation

HRID 1748629 reaction equation
[OH-].[Na+].C(O[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[S:11][CH:12]=1)=[O:7])C.Cl.[CH3:24][C:25]1[CH:26]=[C:27]([NH2:43])[CH:28]=[N:29][C:30]=1[C:31]1[CH2:36][CH2:35][CH:34]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH2:33][CH:32]=1>O1CCCC1.ClCCl.O.C(N(CC)CC)C>[CH3:24][C:25]1[CH:26]=[C:27]([NH:43][C:6]([C:8]2[N:9]=[C:10]([C:13]3[CH:14]=[CH:15][C:16]([C:19]([F:20])([F:21])[F:22])=[CH:17][CH:18]=3)[S:11][CH:12]=2)=[O:7])[CH:28]=[N:29][C:30]=1[C:31]1[CH2:36][CH2:35][CH:34]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH2:33][CH:32]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2737237Ethyl 2-(4-(trifluoromethyl)phenyl)thiazole-4-carboxylateHCID 866924785-Methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-amine

Product 1

HCID 86692567N-{5-Methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-2-[4-(trifluoromethyl) phenyl]thiazole-4-carboxamideYield 61%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

1N Aqueous solution of sodium hydroxide (2 ml) was added at room temperature to a solution of 2-[4-(trifluoromethyl)phenyl]thiazole-4-carboxylic acid ethyl ester (300 mg) described in Reference Example 178 in tetrahydrofuran (2 ml) and stirred at 50° C. for 4.5 hours. After the reaction, 1N aqueous solution of hydrochloric acid (2 ml) was added, the solvent was evaporated and the residue was azeotropically distilled twice with toluene. N,N-Dimethylformamide (catalytic amounts) and thionyl chloride (2 ml) were added to the resulting residue at room temperature, stirred at 80° C. for an hour, and an excess amount of thinly chloride was evaporated. The resulting reaction solution was dissolved in dichloromethane (5 ml), triethylamine (416 μl) and 5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridine-3-amine (327 mg) were added and stirred at room temperature for 20 minutes. After the reaction, water was added, extracted with chloroform and the solvent was evaporated. The resulting residue was purified with a basic silica gel column chromatography (n-hexane/ethyl acetate) to give the titled compound (321 mg) as a white solid.

Workup

  1. additionwas added
  2. customthe solvent was evaporated
  3. distillationthe residue was azeotropically distilled twice with toluene
  4. additionN,N-Dimethylformamide (catalytic amounts) and thionyl chloride (2 ml) were added to the resulting residue at room temperature
  5. stirringstirred at 80° C. for an hour
  6. customan excess amount of thinly chloride was evaporated
  7. customThe resulting reaction solution
  8. stirringstirred at room temperature for 20 minutes
  9. additionwas added
  10. extractionextracted with chloroform
  11. customthe solvent was evaporated
  12. customThe resulting residue was purified with a basic silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-0e277b4ad437445783855ba37b31b7d4
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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