Sodium Bicarbonate → (4-chloro-benzyl)-{5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-carbamic acid tert-butyl ester

HRID 1403259ノート

反応式

HRID 1403259 の反応式
I[C:2]1[C:10]2[CH:9]=[N:8][CH:7]=[N:6][C:5]=2[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:49])[N:32]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=1)[C:33]1[CH:38]=[CH:37][C:36]([CH:39]=[O:40])=[CH:35][N:34]=1)([CH3:29])([CH3:28])[CH3:27].C(=O)(O)[O-].[Na+]>O1CCCC1>[C:26]([O:30][C:31](=[O:49])[N:32]([CH2:41][C:42]1[CH:43]=[CH:44][C:45]([Cl:48])=[CH:46][CH:47]=1)[C:33]1[CH:38]=[CH:37][C:36]([CH:39]([OH:40])[C:2]2[C:10]3[CH:9]=[N:8][CH:7]=[N:6][C:5]=3[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[CH:35][N:34]=1)([CH3:29])([CH3:27])[CH3:28]

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 509865195-Iodo-7-(triisopropylsilyl)-7H-pyrrolo-[2,3-d]pyrimidineHCID 59593313(4-Chloro-benzyl)-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl esterHCID 178418918HCID 178418918、化合物

生成物 1

HCID 57963091(4-chloro-benzyl)-{5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-carbamic acid tert-butyl ester収率 52%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-20 °C

実験手順

5-Iodo-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (38, 0.160 g, 0.4 mmol) was dissolved in 0.7 mL of tetrahydrofuran under an atmosphere of nitrogen. The reaction was cooled to −20° C. and isopropylmagnesium chloride (0.24 mL, 2.0 M in tetrahydrofuran, 0.48 mmol) was added and the reaction was stirred and allowed to come to 0° C. The reaction was cooled to −20° C. and (4-chloro-benzyl)-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (13, 0.110 g, 0.32 mmol) in 2.0 mL of tetrahydrofuran was added to the reaction mixture. The reaction was stirred, allowing to come to 0° C., then poured into aqueous saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with a gradient of 10-80% ethyl acetate in hexanes. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (43, 0.103 g, 52%). MS (ESI) [M+H+]+=622.94.

後処理

  1. customto come to 0° C
  2. temperatureThe reaction was cooled to −20° C.
  3. stirringThe reaction was stirred
  4. customto come to 0° C.
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under vacuum
  10. customThe resulting material was purified by silica gel column chromatography
  11. washeluting with a gradient of 10-80% ethyl acetate in hexanes
  12. concentrationconcentrated under vacuum

出典と根拠

ORDレコード
ord-6a8c196bd6564daa88ae33eb231e21a9
出典データセット
uspto-grants-2014_12
特許番号
US08912204B2

反応ノート

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