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 2389251노트

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HRID 2389251 반응식
[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

참가 물질

10

반응물 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

생성물 1

HCID 672869614-Chloro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(methylsulfonyl)benzamide hydrochloride수율 140.9%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매2회HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-423b3c4444fc41779546455cc5cca48a
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273742B2

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