Acetonitrile → 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide

HRID 51564

反応式

HRID 51564 の反応式
[CH:1]([NH:4]C(C)C)(C)[CH3:2].C([Li])CCC.C(#N)C.[NH2:16][C:17]1[C:18]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:28][CH:27]=3)=[CH:24][N:23]([CH:39]3[CH2:44][CH2:43][C:42](=[O:45])[CH2:41][CH2:40]3)[C:19]=2[N:20]=[CH:21][N:22]=1>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[NH2:16][C:17]1[C:18]2[C:25]([C:26]3[CH:27]=[CH:28][C:29]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:30][CH:31]=3)=[CH:24][N:23]([CH:39]3[CH2:40][CH2:41][C:42]([CH2:2][C:1]#[N:4])([OH:45])[CH2:43][CH2:44]3)[C:19]=2[N:20]=[CH:21][N:22]=1

参加物

7

反応物 4

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 22736171Protein kinase inhibitor 9HCID 178418339Butyllithium

生成物 1

HCID 227362434-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide収率 15,200%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 12679Hexamethylphosphoramide溶媒

反応条件

温度
0 °C

実験手順

A solution of diisopropylamine (0.649 g, 0.0050 mol) in tetrahydrofuran (10 mL) was cooled to 0° C. A solution of 1.6 M n-butyl lithium (3.14 mL, 0.0050 mol) in hexanes was added dropwise, keeping the temperature less than 5° C. After the addition was complete, the mixture was stirred for 20 minutes at 0° C. The mixture was cooled to −78° C., and dry acetonitrile (0.175 g, 0.0043 mol) was added, keeping the temperature less than −70° C. After the addition was complete, the mixture was stirred for 20 minutes at −78° C., and a mixture of 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclohexanone (1.000 g, 0.0025 mmol) in tetrahydrofuran (10 mL) and hexamethylphosphoramide (10 mL) was added, keeping the temperature less than −70° C. After the addition was complete, the mixture was stirred for 30 minutes at −78° C., then stirred at ambient temperature for 18 hours. The mixture was partitioned between dichloromethane and saturated ammonium chloride (aq). The organic phase was washed with water and saturated sodium bicarbonate (aq), and dried over magnesium sulfate. The solvent was removed in vacuo and the cis and trans isomers were separated by flash column chromatography on silica using dichloromethane/methanol (95:5) as an eluent to give less polar 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide (0.120 g, 0.00027 mol) and more polar 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide (0.170 g, 0.00038 mol):

後処理

  1. customthe temperature less than 5° C
  2. additionAfter the addition
  3. temperatureThe mixture was cooled to −78° C.
  4. customthe temperature less than −70° C
  5. additionAfter the addition
  6. stirringthe mixture was stirred for 20 minutes at −78° C.
  7. additionwas added
  8. customthe temperature less than −70° C
  9. additionAfter the addition
  10. stirringthe mixture was stirred for 30 minutes at −78° C.
  11. stirringstirred at ambient temperature for 18 hours
  12. customThe mixture was partitioned between dichloromethane and saturated ammonium chloride (aq)
  13. washThe organic phase was washed with water and saturated sodium bicarbonate (aq)
  14. dry with materialdried over magnesium sulfate
  15. customThe solvent was removed in vacuo
  16. customthe cis and trans isomers were separated by flash column chromatography on silica

出典と根拠

ORDレコード
ord-0dfd4308f6d54cbd9db5af920712d17a
出典データセット
uspto-grants-2004_03
特許番号
US06713474B2

関連ノート

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