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 1748629노트

반응식

HRID 1748629 반응식
[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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

반응 조건

온도
50 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-0e277b4ad437445783855ba37b31b7d4
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150555B2

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