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

HRID 1364116

Reaktionsgleichung

Reaktionsgleichung von HRID 1364116
[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

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 27627062-Bromopyridine-5-boronic acidHCID 178420305HCID 178420305, Verbindung

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8895Cupric acetateKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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%)

Quellen und Nachweise

ORD-Eintrag
ord-3ea1c5702c6e4fe8acb59c57d1a68e12
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07888347B2

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