Methanol → [8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl]methanol

HRID 928602

반응식

HRID 928602 반응식
[Br:1][C:2]1[C:10]2[C:9](Cl)=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1.[CH:12]12[NH:19][CH:16]([CH2:17][CH2:18]1)[CH2:15][CH:14]([CH2:20][OH:21])[CH2:13]2.C(=O)([O-])[O-].[K+].[K+].CO>C(#N)C.ClCCl>[Br:1][C:2]1[C:10]2[C:9]([N:19]3[CH:12]4[CH2:18][CH2:17][CH:16]3[CH2:15][CH:14]([CH2:20][OH:21])[CH2:13]4)=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1

참가 물질

7

반응물 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 454802995-Bromo-4-chlorothieno[2,3-d]pyrimidineHCID 457926978-Azabicyclo[3.2.1]octan-3-ylmethanol

생성물 1

HCID 117739109[8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl]methanol수율 91.5%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

5-Bromo-4-chloro-thieno[2,3-d]pyrimidine (1.0 g, 4.0 mmol) in acetonitrile (25 mL) was treated with 8-azabicyclo[3.2.1]octan-3-ylmethanol (705 mg, 16 mmol) and potassium carbonate (2.208 g, 16 mmol) at reflux for 4 h. The reaction was then concentrated in vacuum to a gum and partitioned between ethyl acetate (100 mL) and water (50 mL). The ethyl acetate was separated, dried over sodium sulphate and concentrated in vacuum to give a yellow gum. The gum was columned on silica in a gradient of 2-8% methanol in dichloromethane on a 100 g column. The main first fraction was collected and concentrated in vacuum to a gum. The gum was triturated with diethyl ether (20 mL) and crystallized on standing for a few minutes. The diethyl ether was decanted off and the crystals dried in vacuum to yield 3 [8-(5-bromothieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl]methanol (1.297 g, 3.66 mmol, 91%). 1H NMR (CDCl3) δ: 1.42 (2H, dd, J=12 Hz, J′=4 Hz), 1.67 (2H, d, J=4 Hz), 1.82 (1H, br s), 1.98 (3H, br m), 2.48 (2H, quintet, J=4 Hz), 3.64 (2H, d, J=4 Hz), 4.7 (2H, br s), 7.32 (1H, s), 8.45 (1H, s).

후처리

  1. temperatureat reflux for 4 h
  2. concentrationThe reaction was then concentrated in vacuum to a gum
  3. custompartitioned between ethyl acetate (100 mL) and water (50 mL)
  4. customThe ethyl acetate was separated
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuum
  7. customto give a yellow gum
  8. customThe main first fraction was collected
  9. concentrationconcentrated in vacuum to a gum
  10. customThe gum was triturated with diethyl ether (20 mL)
  11. customcrystallized
  12. waiton standing for a few minutes
  13. customThe diethyl ether was decanted off
  14. customthe crystals dried in vacuum

출처 및 근거

ORD 기록
ord-6a7de14c51f94896976921ed3ca4f657
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290511B2

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