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

HRID 928602

反応式

HRID 928602 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-6a7de14c51f94896976921ed3ca4f657
出典データセット
uspto-grants-2016_03
特許番号
US09290511B2

関連ノート

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