Diisopropylethylamine → 1-[4-(Cyanomethyl)-1-pyrimidin-4-ylpiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide

HRID 521232ノート

反応式

HRID 521232 の反応式
FC(F)(F)C([O-])=O.[C:8]([C:11]1[C:12]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:13][N:14]([C:16]2([CH2:22][C:23]#[N:24])[CH2:21][CH2:20][NH2+:19][CH2:18][CH2:17]2)[CH:15]=1)(=[O:10])[NH2:9].CCN(C(C)C)C(C)C.Br[C:43]1[CH:48]=[CH:47][N:46]=[CH:45][N:44]=1>ClCCCl.C(Cl)Cl.CC(O)C>[C:23]([CH2:22][C:16]1([N:14]2[CH:15]=[C:11]([C:8]([NH2:9])=[O:10])[C:12]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[N:13]2)[CH2:21][CH2:20][N:19]([C:43]2[CH:48]=[CH:47][N:46]=[CH:45][N:44]=2)[CH2:18][CH2:17]1)#[N:24]

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 127522204-BromopyrimidineHCID 867294014-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidin-1-ium 2,2,2-trifluoroacetate2 回

生成物 1

HCID 867294031-[4-(Cyanomethyl)-1-pyrimidin-4-ylpiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
130 °C

実験手順

To a solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (50 mg, 0.11 mmol) in DCE (1.0 mL) was added DIPEA (0.096 mL, 0.55 mmol) followed by 4-bromopyrimidine (32 mg, 0.16 mmol). The reaction mixture was heated under microwave irradiation to 130° C. and allowed to stir for 15 minutes. The reaction mixture was then cooled to ambient temperature and diluted with a mixture of DCM and IPA. The resulting mixture was sequentially washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting residue was purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound, Example #26, as a solid.

後処理

  1. temperatureThe reaction mixture was then cooled to ambient temperature
  2. washThe resulting mixture was sequentially washed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse-phase preparative HPLC (MeCN/water
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-3ac2d48f348e48029c4522b5908a662c
出典データセット
uspto-grants-2016_05
特許番号
US09328099B2

反応ノート

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