Chlorotrimethylsilane → 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile

HRID 1778429ノート

反応式

HRID 1778429 の反応式
[CH3:1][C:2]([N:6]1[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]1)([CH3:5])[CH:3]=O.N1CCCC1.[Si](Cl)(C)(C)C.[NH2:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]2[N:30]([CH2:47][C@@H:48]3[CH2:52][CH2:51][CH2:50][N:49]3[C:53](=[O:57])[CH2:54][C:55]#[N:56])[N:31]=[C:32]([C:33]3[CH:38]=[CH:37][C:36]([O:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[CH:35][C:34]=3[F:46])[C:25]=12>CC#N.C(Cl)Cl.O>[NH2:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]2[N:30]([CH2:47][C@@H:48]3[CH2:52][CH2:51][CH2:50][N:49]3[C:53]([C:54](=[CH:3][C:2]([CH3:5])([N:6]3[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]3)[CH3:1])[C:55]#[N:56])=[O:57])[N:31]=[C:32]([C:33]3[CH:38]=[CH:37][C:36]([O:39][C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)=[CH:35][C:34]=3[F:46])[C:25]=12

参加物

8

反応物 4

HCID 6397ChlorotrimethylsilaneHCID 31268PyrrolidineHCID 86714506(S)-3-(2-((4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidin-1-yl)-3-oxopropanenitrileHCID 900010212-Methyl-2-(4-methylpiperazin-1-yl)propanal

生成物 1

HCID 1236017872-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile収率 71%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of 2-methyl-2-(4-methylpiperazin-1-yl)propanal (108.3 mg, 0.6400 mmol) in MeCN (6 mL), was added pyrrolidine (0.11 mL, 1.27 mmol). The reaction mixture was cooled to 0° C., followed by the addition TMS-Cl (0.11 mL, 0.85 mmol). The ice bath was removed and the mixture stirred for 10 min before adding 3-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidin-1-yl]-3-oxo-propanenitrile (100 mg, 0.210 mmol). The mixture was stirred for 3 h at room temperature, checking progress by TLC and LC-MS. To the mixture was added 15 ml water and extracted with dichloromethane. The combined organic layer was washed by brine, dried over by Na2SO4, filtered, and evaporated. The residues was loaded on TLC plate and purified using MeOH:CH2Cl2=9:100 to get pure product 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile (93 mg, 0.1491 mmol, 70.30 2% yield) as a light yellow powder. LC-MS (ES, m/z): 625 [M+H].

後処理

  1. customThe ice bath was removed
  2. stirringThe mixture was stirred for 3 h at room temperature
  3. extractionextracted with dichloromethane
  4. washThe combined organic layer was washed by brine
  5. dry with materialdried over by Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. custompurified

出典と根拠

ORDレコード
ord-205199ebbc05427bba492e24e2d46f56
出典データセット
uspto-grants-2016_02
特許番号
US09266895B2

反応ノート

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