Furan, 2-bromo- → 2-Furanyl(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-en-7-yl)methanone

HRID 218067

Reaction equation

HRID 218067 reaction equation
Br[C:2]1[O:3][CH:4]=[CH:5][CH:6]=1.[Li]CCCC.CON(C)[C:15]([C:17]1[CH2:24][CH:23]2[CH:19]([CH2:20][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22]2)[CH:18]=1)=[O:16]>C1COCC1>[O:3]1[CH:4]=[CH:5][CH:6]=[C:2]1[C:15]([C:17]1[CH2:24][CH:23]2[CH:19]([CH2:20][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22]2)[CH:18]=1)=[O:16]

Participants

5

Reactant 3

HCID 2776190Furan, 2-bromo-HCID 86643297N-methoxy-N-methyl-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-ene-7-carboxamideHCID 178418339Butyllithium

Product 1

HCID 684695122-Furanyl(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-en-7-yl)methanoneYield 50.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-bromofuran (0.11 g, 0.74 mmol) in THF (3 mL) at −78° C. was added n-BuLi solution (2.5 M solution in hexanes, 0.30 mL, 0.75 mmol) and the mixture was stirred for 1 h. A solution of N-methoxy-N-methyl-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-ene-7-carboxamide (0.20 g, 0.65 mmol) in THF (2 mL) was added, and the mixture was warmed to ambient temperature over 8 h. The reaction was quenched with water (0.2 mL), diluted with of ethyl (20 mL) acetate, dried over anhydrous sodium sulfate and concentrated by rotary evaporation. The crude product was purified on silica gel column chromatography to obtain 0.10 g of 2-furanyl(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-en-7-yl)methanone and 0.06 g of recovered starting material. A sample of 2-furanyl(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-en-7-yl)methanone (0.050 g, 0.16 mmol) was dissolved in dichloromethane (3 mL), treated with TFA (2.0 mL), and stirred at ambient temperature for 1 h. The volatiles were evaporated, and the product was vacuum dried to obtain 0.047 g of 2-furanyl(3-azabicyclo[3.3.0]oct-6-en-7-yl)methanone trifluoroacetate (1H NMR (CD3OD, 300 MHz): δ 7.81-7.80 (m, 1H), 7.38-7.36 (m, 1H), 6.91-6.88 (m, 1H), 6.65 (dd, J=3.66, 1.71 Hz), 3.95-3.86 (m, 1H), 3.56-3.40 (m, 3H), 3.27-3.16 (m, 1H), 3.14-3.02 (m, 2H), 2.77-2.68 (m, 1H); MS (m/z): 204 (M+1)). This material exhibited Ki values at rat and human α4β2 of 8 nM and 2 nM respectively and did not pass HTS for α7.

Workup

  1. customThe reaction was quenched with water (0.2 mL)
  2. additiondiluted with of ethyl (20 mL) acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated by rotary evaporation
  5. customThe crude product was purified on silica gel column chromatography

Sources & evidence

ORD record
ord-a0a10005b1244b7f9d93f62d8c63e6c0
Source dataset
uspto-grants-2012_06
Patent number
US08198296B2

Linked notes

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