Dichloromethane → (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile

HRID 1429748ノート

反応式

HRID 1429748 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31](=[O:35])[CH2:32][C:33]#[N:34])[CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][C:12]=3[F:24])[C:3]=12.[OH:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]([CH3:47])([CH3:46])[CH:44]=O)[CH2:39][CH2:38]1.N1CCCC1.C(Cl)Cl>C([O-])(O)=O.[Na+]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31]([C:32](=[CH:47][C:43]([N:40]4[CH2:41][CH2:42][CH:37]([OH:36])[CH2:38][CH2:39]4)([CH3:44])[CH3:46])[C:33]#[N:34])=[O:35])[CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:13][C:12]=3[F:24])[C:3]=12

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 31268PyrrolidineHCID 867144983-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrileHCID 900010502-(4-Hydroxy-1-piperidyl)-2-methyl-propanal

生成物 1

HCID 123595811(R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile収率 32%

試薬・触媒・溶媒 1

HCID 516892Sodium Bicarbonate溶媒

実験手順

A mixture of (R)-3-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-3-oxopropanenitrile (150 mg, 0.31 mmol), 2-(4-hydroxy-1-piperidyl)-2-methyl-propanal (167 mg, 0.98 mmol), pyrrolidine (0.03 mL, 0.31 mmol) and DCM (10 mL) was stirred at room temp for 2 days and then diluted with aq. NaHCO3 (40 mL) and extracted with DCM. The organic was dried (MgSO4), filtered and concentrated to an oil. The crude material was purified at Isolera (25 g column: 30% iPrOH/DCM) to obtain the product which was isolated by lyophilization to provide 61 mg (32% yield) of (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile as a powder. MS (pos. ion) m/z: 625 (M+1).

後処理

  1. extractionextracted with DCM
  2. dry with materialThe organic was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to an oil
  5. customThe crude material was purified at Isolera (25 g column: 30% iPrOH/DCM)
  6. customto obtain the product which
  7. customwas isolated by lyophilization

出典と根拠

ORDレコード
ord-5e1b549d83b04a8dab2ead1714cea0f4
出典データセット
uspto-grants-2015_01
特許番号
US08940744B2

反応ノート

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