Dimethylformamide → 5-Amino-N-{2-[({[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}amino)methyl]-3,3,3-trifluoro-2-hydroxypropyl}-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 886729

반응식

HRID 886729 반응식
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[C:3]=1[C:4]([OH:6])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[N:31]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[N:30]=[CH:29][C:28]=1[C:39]([NH:41][CH2:42][C:43]([CH2:49][NH2:50])([OH:48])[C:44]([F:47])([F:46])[F:45])=[O:40]>O1CCCC1.C(N(C(C)C)CC)(C)C>[NH2:26][C:27]1[N:31]([C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[N:30]=[CH:29][C:28]=1[C:39]([NH:41][CH2:42][C:43]([CH2:49][NH:50][C:4]([C:3]1[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:8][CH:9]=[CH:10][C:2]=1[Cl:1])=[O:6])([OH:48])[C:44]([F:47])([F:46])[F:45])=[O:40]

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 111279652-chloro-6-(trifluoromethyl)benzoic AcidHCID 594874945-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

생성물 1

HCID 594874885-Amino-N-{2-[({[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}amino)methyl]-3,3,3-trifluoro-2-hydroxypropyl}-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide수율 88.4%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매3회HCID 81531Diisopropylethylamine용매

실험 절차

To a solution of 2-chloro-6-(trifluoromethyl)benzoic acid (27 mg) in anhydrous tetrahydrofuran (1 ml) was added anhydrous dimethylformamide (5 μl) followed by a solution of oxalyl chloride in anhydrous tetrahydrofuran (1M, 0.13 ml). The solution effervesced and was stirred under nitrogen for 30 minutes. A solution of 5-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (36 mg) in anhydrous tetrahydrofuran (1 ml) and diisopropylethylamine (65 μl) was added washed in with further tetrahydrofuran (0.5 ml). It was stirred under nitrogen for 16 hours, blown down, dissolved in dichloromethane (5 ml), washed with 2M hydrochloric acid (2 ml), blown down and purified on a silica SPE cartridge (5 g). Elution with dichloromethane followed by ethyl acetate:cyclohexane (1:5), (1:3), (1:2), (1:1) (4 times). Combination of the appropriate fractions and evaporation gave the title compound (50 mg).

후처리

  1. washwashed in with further tetrahydrofuran (0.5 ml)
  2. stirringIt was stirred under nitrogen for 16 hours
  3. dissolutiondissolved in dichloromethane (5 ml)
  4. washwashed with 2M hydrochloric acid (2 ml)
  5. custompurified on a silica SPE cartridge (5 g)
  6. washElution with dichloromethane
  7. customCombination of the appropriate fractions and evaporation

출처 및 근거

ORD 기록
ord-8895ef5f760244929c1ee44137670092
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247377B2

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