2,6-Dichlorobenzoyl chloride → 5-Amino-N-[2-({[(2,6-dichlorophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 886720

Reaktionsgleichung

Reaktionsgleichung von HRID 886720
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([CH2:24][NH2:25])([OH:23])[C:19]([F:22])([F:21])[F:20])=[O:15].C(N(C(C)C)CC)(C)C.[Cl:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]([Cl:45])[C:37]=1[C:38](Cl)=[O:39]>O1CCCC1>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([CH2:24][NH:25][C:38]([C:37]1[C:36]([Cl:35])=[CH:44][CH:43]=[CH:42][C:41]=1[Cl:45])=[O:39])([OH:23])[C:19]([F:22])([F:21])[F:20])=[O:15]

Komponenten

5

Edukt 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 594874945-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

Produkt 1

HCID 236494655-Amino-N-[2-({[(2,6-dichlorophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
21 °C

Versuchsvorschrift

To a solution of 5-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (0.93 g, 2.57 mmol) in anhydrous tetrahydrofuran (12 ml) was added diisopropylethylamine (0.91 ml, 5.2 mmol) followed by 2,6-dichlorobenzoyl chloride (0.38 ml, 1.05 equiv). There was an immediate exotherm and therefore the mixture was placed in an ice/solid carbon dioxide bath for 20 minutes and then stirred at 21° C. for 17 hours. It was then partitioned between ethyl acetate (100 ml) and 2M hydrochloric acid (20 ml) and the organic phase was washed with water (20 ml), saturated brine (20 ml), saturated sodium bicarbonate (20 ml), water (20 ml) and saturated brine (20 ml) before being dried over magnesium sulphate and evaporated under reduced pressure to give a foam. This was purified on a Flashmaster column of silica (100 g) with a gradient of 0-100% ethyl acetate in cyclohexane over 60 minutes to give the title compound (1.07 g).

Aufarbeitung

  1. customIt was then partitioned between ethyl acetate (100 ml) and 2M hydrochloric acid (20 ml)
  2. washthe organic phase was washed with water (20 ml), saturated brine (20 ml), saturated sodium bicarbonate (20 ml), water (20 ml) and saturated brine (20 ml)
  3. dry with materialbefore being dried over magnesium sulphate
  4. customevaporated under reduced pressure
  5. customto give a foam
  6. customThis was purified on a Flashmaster column of silica (100 g) with a gradient of 0-100% ethyl acetate in cyclohexane over 60 minutes

Quellen und Nachweise

ORD-Eintrag
ord-638c01ecf1f74151b4d7c511c85493f5
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08247377B2

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