Hydrochloric Acid → 4-Chloro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(methylsulfonyl)benzamide hydrochloride

HRID 1466224Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1466224
[CH3:1][NH:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]3[N:23]([CH3:24])[N:22]=[CH:21][CH:20]=3)=[N:11][N:10]=2)[CH2:5][CH2:4]1.[Cl:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[C:28]([S:35]([CH3:38])(=[O:37])=[O:36])[CH:27]=1.C(N(C(C)C)CC)(C)C.C1(P(C2C=CC=CC=2)(=O)OC2C(F)=C(F)C(F)=C(F)C=2F)C=CC=CC=1.Cl.C(OCC)C>CN(C=O)C.C(Cl)Cl.CS(C)=O>[ClH:25].[Cl:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([N:2]([CH3:1])[CH:3]2[CH2:4][CH2:5][N:6]([C:9]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12]([C:19]4[N:23]([CH3:24])[N:22]=[CH:21][CH:20]=4)=[N:11][N:10]=3)[CH2:7][CH2:8]2)=[O:32])=[C:28]([S:35]([CH3:38])(=[O:37])=[O:36])[CH:27]=1

Komponenten

10

Edukt 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 27610554-Chloro-2-(methylsulfonyl)benzoic acidHCID 4652311Pentafluorophenyl diphenylphosphinateHCID 59627388N-methyl-1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-amine

Produkt 1

HCID 672869614-Chloro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(methylsulfonyl)benzamide hydrochlorideAusbeute 140,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittel2×HCID 6228DimethylformamideLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Dissolve N-methyl-1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-amine (100 mg, 0.31 mmol), 4-chloro-2-(methylsulfonyl)benzoic acid (87 mg, 0.37 mmol) and diisopropylethylamine (0.26 mL, 1.5 mmol) in DMF:DMSO=4:1 (2 mL) at 60° C. Cool to 0° C. and add pentafluorophenyl diphenylphosphinate (250 mg, 0.65 mmol) in DMF:DMSO=1:1 (1 mL) to the solution. Stir the mixture at 60° C. overnight. Cool the reaction mixture to ambient temperature and dilute with CH2Cl2, wash with brine, dry over Na2SO4, and concentrate under reduced pressure. Purify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate:2 M NH3 in MeOH=20:5:1) to provide the product. Add excess 1 N HCl in diethyl ether (1 mL, 10 mmol) to the isolated product and remove the solvent to provide the title compound (150 mg, 84%). ES/MS m/z 539.0 (M+1).

Aufarbeitung

  1. customat 60° C
  2. temperatureCool the reaction mixture to ambient temperature
  3. washwash with brine
  4. dry with materialdry over Na2SO4
  5. concentrationconcentrate under reduced pressure
  6. customPurify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate:2 M NH3 in MeOH=20:5:1)
  7. customto provide the product

Quellen und Nachweise

ORD-Eintrag
ord-5af5c032c76b47dfb0ce99ed46f0d6d7
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09000023B2

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