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 1403259노트

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HRID 1403259 반응식
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]

참가 물질

6

반응물 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, 화합물

생성물 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 ester수율 52%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-20 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6a8c196bd6564daa88ae33eb231e21a9
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08912204B2

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