Pyridine → 2-(6-Bromo-3-pyridinyl)-6-(phenylmethyl)-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine

HRID 1364116ノート

反応式

HRID 1364116 の反応式
[C:1]1([CH2:7][N:8]2[CH2:14][CH2:13][C:12]3=[CH:15][NH:16][N:17]=[C:11]3[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:18][C:19]1[N:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:18][C:19]1[N:24]=[CH:23][C:22]([N:16]2[CH:15]=[C:12]3[C:11]([CH2:10][CH2:9][N:8]([CH2:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:14][CH2:13]3)=[N:17]2)=[CH:21][CH:20]=1

参加物

6

反応物 3

HCID 1049PyridineHCID 27627062-Bromopyridine-5-boronic acidHCID 178420305HCID 178420305、化合物

生成物 1

HCID 866216752-(6-Bromo-3-pyridinyl)-6-(phenylmethyl)-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 6-(phenylmethyl)-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (may be prepared as described in Description 5) (200 mg, 0.88 mmol), (6-bromo-3-pyridinyl)boronic acid (355 mg, 1.76 mmol), copper acetate (478 mg, 2.64 mmol), pyridine (0.142 ml, 1.76 mmol) and molecular sieves (600 mg) in dichloromethane (10 ml) was allowed to stir at room temperature in a flask open to the atmosphere for 240 hours. The reaction mixture was filtered through a pad of celite, washing with dichloromethane and methanol. The filtrate was evaporated, redissolved in methanol and passed down a 10 g SCX cartridge, eluting with methanol, then a 2 M solution of ammonia in methanol. The basic fractions were combined, evaporated and purified by column chromatography, eluting with a mixture of 2M ammonia in methanol and dichloromethane (0-10%). The impure product was re-purified using reverse phase chromatography, eluting with a mixture of acetonitrile and water (5-100% and 3-60%) to afford the product (D15); MS (ES+) m/e 383 & 385 [M+H]+.

後処理

  1. filtrationThe reaction mixture was filtered through a pad of celite
  2. washwashing with dichloromethane and methanol
  3. customThe filtrate was evaporated
  4. dissolutionredissolved in methanol
  5. washeluting with methanol
  6. customevaporated
  7. custompurified by column chromatography
  8. washeluting with a mixture of 2M ammonia in methanol and dichloromethane (0-10%)
  9. customThe impure product was re-purified
  10. washeluting with a mixture of acetonitrile and water (5-100% and 3-60%)

出典と根拠

ORDレコード
ord-3ea1c5702c6e4fe8acb59c57d1a68e12
出典データセット
uspto-grants-2011_02
特許番号
US07888347B2

反応ノート

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