Water → 4-(5-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1993695ノート

反応式

HRID 1993695 の反応式
ClC(Cl)(Cl)C[O:4][C:5](=O)[NH:6][C:7]1[N:8]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:9]=[C:10]([C:12]([CH2:16][F:17])([CH3:15])[CH2:13][F:14])[CH:11]=1.CCN(C(C)C)C(C)C.[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][N:47]([C:50]2[CH:55]=[CH:54][C:53]([NH2:56])=[C:52]([CH3:57])[N:51]=2)[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38].O>CS(C)=O>[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][N:47]([C:50]2[CH:55]=[CH:54][C:53]([NH:56][C:5]([NH:6][C:7]3[N:8]([C:18]4[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=4)[N:9]=[C:10]([C:12]([CH2:13][F:14])([CH3:15])[CH2:16][F:17])[CH:11]=3)=[O:4])=[C:52]([CH3:57])[N:51]=2)[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38]

参加物

6

反応物 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 591344511-Boc-4-(5-amino-6-methyl-2-pyridinyl)piperazineHCID 68538054[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

生成物 1

HCID 685370594-(5-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
85 °C

実験手順

Add [5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester (2.7 mmol, 1.2 g) and DIEA (2.9 mmol, 0.5 mL) over a solution of 4-(5-amino-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (2.9 mmol, 0.9 g) in 4 mL of DMSO and stir at 85° C. overnight. Cool down, add water and extract with CH2Cl2. Combine the organic layers and wash with saturated aq. sodium chloride solution. Dry over sodium sulfate, filter, and concentrate under reduced pressure to give 4-(5-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-6-methyl-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester. Subject residue to silica gel chromatography eluting with hexanes/ethyl acetate in gradient (from 10 to 50%). MS(ES+): m/z=584 [M+H]).

後処理

  1. temperatureCool down,
  2. extractionextract with CH2Cl2
  3. washwash with saturated aq. sodium chloride solution
  4. dry with materialDry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure

出典と根拠

ORDレコード
ord-e96b4fe7c4a4476bacea41cb81ea353f
出典データセット
uspto-grants-2010_01
特許番号
US07652015B2

反応ノート

読み込み中…