Trimethylsilyldiazomethane → Methyl 1-{[1-(3-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}cyclopentane-carboxylate

HRID 1776710Notes

Reaction equation

HRID 1776710 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[CH2:5][NH:6][C:7]1[C:8]([NH2:25])=[CH:9][C:10]([O:13][CH2:14][C:15]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=2)=[CH:11][CH:12]=1.[C:29]1(=[O:39])[C:33]2([CH2:37][CH2:36][CH2:35][CH2:34]2)[CH2:32][C:31](=O)[O:30]1.[Si](C=[N+]=[N-])(C)(C)[CH3:41]>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[CH2:5][N:6]1[C:7]2[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:9][C:8]=2[N:25]=[C:41]1[CH2:32][C:33]1([C:29]([O:30][CH3:31])=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 167693TrimethylsilyldiazomethaneHCID 27371022-oxaspiro[4.4]nonane-1,3-dioneHCID 90414557N1-(3-bromobenzyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine

Product 1

HCID 90414509Methyl 1-{[1-(3-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}cyclopentane-carboxylateYield 79.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N1-(3-bromobenzyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine (1.0 g, 2.4 mmol) in acetonitrile (20 mL) was added 2-oxaspiro[4.4]nonane-1,3-dione (420 mg, 2.7 mmol) and the solution heated to 80° C. for 8 h. The solution was cooled to RT and concentrated to dryness. To this residue was added acetic acid (15 mL) and the resulting solution was heated to 80° C. for 3 h. The solution was cooled, concentrated to dryness and the resulting residue was taken up in toluene/MeOH (15 mL; 3:1). The solution was treated with TMSCHN2 (1.5 mL, 3 mmol, 2 M in hexanes) dropwise (bubbling observed). The mixture was stirred at RT for 30 min and then concentrated to dryness. The residue was purified using FCC to provide 1.12 g of the title compound. MS (ESI): mass calcd. for C32H30BrN3O3, 583.15; m/z found, 584.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=8.5, 1H), 8.09 (d, J=8.7, 1H), 7.82 (d, J=8.2, 1H), 7.75-7.69 (m, 2H), 7.56-7.52 (m, 1H), 7.40 (d, J=7.9, 1H), 7.35 (d, J=2.2, 1H), 7.20 (s, 1H), 7.18-7.14 (m, 1H), 7.05-7.02 (m, 1H), 6.99-6.96 (m, 1H), 6.89-6.86 (m, 1H), 5.42 (s, 2H), 5.33 (s, 2H), 3.62 (s, 3H), 3.08 (s, 2H), 2.26-2.20 (m, 2H), 1.87-1.80 (m, 2H), 1.77-1.64 (m, 4H); 584.0 (M+H) m/z

Workup

  1. temperatureThe solution was cooled to RT
  2. concentrationconcentrated to dryness
  3. additionTo this residue was added acetic acid (15 mL)
  4. temperaturethe resulting solution was heated to 80° C. for 3 h
  5. temperatureThe solution was cooled
  6. concentrationconcentrated to dryness
  7. concentrationconcentrated to dryness
  8. customThe residue was purified

Sources & evidence

ORD record
ord-0c4112b4efc7483cbda1e07fecd0843f
Source dataset
uspto-grants-2016_02
Patent number
US09265770B2

Reaction notes

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