Borane;tetrahydrofuran → HCID 136348448, compound

HRID 1748781Notes

Reaction equation

HRID 1748781 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:14][CH2:13][C:12](=O)[NH:11][C:10]3[N:16]([CH2:25][CH3:26])[N:17]=[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1.O1CCCC1.B>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:14][CH2:13][CH2:12][NH:11][C:10]3[N:16]([CH2:25][CH3:26])[N:17]=[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 136348447HCID 136348447, compound

Product 1

HCID 136348448HCID 136348448, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-4,5,6,8-tetrahydropyrazolo[3,4-b]azepin-7(1H)-one (0.045 g, 0.11 mmol, Example #AA.1) in THF (2 mL) was added borane tetrahydrofuran complex (1M in THF, 0.74 mL, 0.74 mmol) and the reaction was stirred at rt for about 2 h. The reaction was cooled to 0° C. and carefully quenched with 5M HCl (1 mL) and then stirred about 30 min at rt. The organic solvents were removed in vacuo and the aqueous layer was neutralized with solid Na2CO3 and extracted with EtOAc (2×10 mL). The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was further purified by silica gel column chromatography using a gradient of 65-85% EtOAc in heptane. Product fractions were combined and concentrated in vacuo. The residue was dissolved in ACN (2 mL) and the product was precipitated by addition of water. The product was filtered off and dried in the vacuum oven at about 50° C. to yield 4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepine as an off-white solid (0.030 g, 0.073 mmol, 69%); LC-MS (Table 1, Method g) Rt=2.72 min, m/z 411/413 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.44-8.39 (m, 1H), 7.77-7.72 (m, 1H), 7.68-7.61 (m, 1H), 7.24 (d, J=2.1 Hz, 1H), 7.16-7.09 (m, 2H), 6.92 (d, J=8.3 Hz, 1H), 5.70 (t, J=3.9 Hz, 1H), 5.66-5.58 (m, 1H), 4.13-3.97 (m, 2H), 3.40-3.30 (m, 1H), 2.84-2.74 (m, 1H), 2.45 (s, 3H), 1.92-1.82 (m, 1H), 1.81-1.70 (m, 1H), 1.68-1.57 (m, 1H), 1.57-1.45 (m, 1H), 1.28 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customcarefully quenched with 5M HCl (1 mL)
  3. stirringstirred about 30 min at rt
  4. customThe organic solvents were removed in vacuo
  5. extractionextracted with EtOAc (2×10 mL)
  6. dry with materialThe combined extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was further purified by silica gel column chromatography
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in ACN (2 mL)
  12. customthe product was precipitated by addition of water
  13. filtrationThe product was filtered off
  14. customdried in the vacuum oven at about 50° C.

Sources & evidence

ORD record
ord-92501a6aa8304359a7a038ccb3a49494
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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