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 2389251ノート

反応式

HRID 2389251 の反応式
[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

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-423b3c4444fc41779546455cc5cca48a
出典データセット
uspto-grants-2012_09
特許番号
US08273742B2

反応ノート

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