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

Reaktionsgleichung

Reaktionsgleichung von HRID 886729
[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]

Komponenten

7

Edukt 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

Produkt 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-carboxamideAusbeute 88,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel3×HCID 81531DiisopropylethylamineLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8895ef5f760244929c1ee44137670092
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08247377B2

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