Triethylamine → 1-(Cyclopropylmethyl)-3-(4-(4-((5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)thiazol-2-yl)methyl)piperazine-1-carbonyl)phenyl)urea

HRID 1807809노트

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HRID 1807809 반응식
[F:1][C:2]([F:17])([F:16])[C:3]([C:9]1[S:13][C:12]([CH2:14]O)=[N:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].C(N(CC)CC)C.CS(Cl)(=O)=O.[CH:30]1([CH2:33][NH:34][C:35]([NH:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]([N:46]3[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]3)=[O:45])=[CH:40][CH:39]=2)=[O:36])[CH2:32][CH2:31]1.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH:30]1([CH2:33][NH:34][C:35]([NH:37][C:38]2[CH:39]=[CH:40][C:41]([C:44]([N:46]3[CH2:51][CH2:50][N:49]([CH2:14][C:12]4[S:13][C:9]([C:3]([OH:8])([C:4]([F:7])([F:6])[F:5])[C:2]([F:17])([F:16])[F:1])=[CH:10][N:11]=4)[CH2:48][CH2:47]3)=[O:45])=[CH:42][CH:43]=2)=[O:36])[CH2:31][CH2:32]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 580558061-(Cyclopropylmethyl)-3-(4-(Piperazine-1-carbonyl)phenyl)ureaHCID 866385861,1,1,3,3,3-Hexafluoro-2-(2-(hydroxymethyl)thiazol-5-yl)propan-2-ol

생성물 1

HCID 591758311-(Cyclopropylmethyl)-3-(4-(4-((5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)thiazol-2-yl)methyl)piperazine-1-carbonyl)phenyl)urea수율 0.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

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온도
0 °C

실험 절차

To a stirring solution of 1,1,1,3,3,3-hexafluoro-2-(2-(hydroxymethyl)thiazol-5-yl)propan-2-ol (0.533 mmol, 150 mg) and triethylamine (1.600 mmol, 162 mg) in dichloromethane (4 mL) at 0° C. was added methanesulfonyl chloride (0.533 mmol, 61.1 mg). The mixture was stirred at 0° C. for 1 hour before warming to room temperature and stirring for 1 hour. The reaction mixture was diluted with dichloromethane (50 mL) and washed with water (2×20 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (4 mL) and 1-(cyclopropylmethyl)-3-(4-(piperazine-1-carbonyl)phenyl)urea (0.635 mmol, 192 mg) was added followed by potassium carbonate (1.905 mmol, 263 mg). The mixture was heated to reflux for 6 hours then was cooled, diluted with dichloromethane (75 mL) and washed with water (2×20 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by HPLC, strong cation exchange column chromatography and silica gel column chromatography (10% methanol/90% dichloromethane) to afford the title compound (1.5 mg).

후처리

  1. temperaturebefore warming to room temperature
  2. stirringstirring for 1 hour
  3. washwashed with water (2×20 mL)
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in acetonitrile (4 mL)
  8. temperatureThe mixture was heated
  9. temperatureto reflux for 6 hours
  10. temperaturethen was cooled
  11. washwashed with water (2×20 mL)
  12. dry with materialThe organic phase was dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customThe resulting residue was purified by HPLC, strong cation exchange column chromatography and silica gel column chromatography (10% methanol/90% dichloromethane)

출처 및 근거

ORD 기록
ord-d4d7aa8a96d74f858c9ee605621a66da
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08357679B2

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