Sodium hydride → Methyl 1-(2-(benzyloxy)ethyl)-2-(2-(benzyloxy)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 860732Notes

Reaction equation

HRID 860732 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[C:16]([C:17]2[NH:18][C:19]3[C:24]([C:25]=2[CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:23][CH:22]=[C:21]([C:32]([O:34][CH3:35])=[O:33])[CH:20]=3)=[CH:15][CH:14]=[CH:13][N:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:37][CH2:38][O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>CN(C=O)C>[CH2:40]([O:39][CH2:38][CH2:37][N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[C:21]([C:32]([O:34][CH3:35])=[O:33])[CH:20]=2)[C:25]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[C:17]1[C:16]1[C:11]([O:10][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[N:12][CH:13]=[CH:14][CH:15]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 73833Benzene, ((2-bromoethoxy)methyl)-HCID 58765212Methyl 2-(2-(benzyloxy)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 58765229Methyl 1-(2-(benzyloxy)ethyl)-2-(2-(benzyloxy)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylateYield 49.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (14 mg of 60% dispersion in mineral oil, 0.354 mmol) in DMF (2 mL), methyl 2-(2-(benzyloxy)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylate (130 mg, 0.295 mmol) was added and the reaction mixture was stirred at rt for 15 min. Benzyl 2-bromoethyl ether (0.052 mL, 0.325 mmol) was then added, and the reaction mixture was stirred at rt overnight before being quenched by the addition of water. The resultant mixture was extracted with ethyl acetate (2×20 mL) and the organic layers were combined, washed with 1N HCl solution, and then dried (MgSO4), filtered and concentrated under vacuum. The residue was then purified by Prep. reverse phase HPLC to give the title compound as light yellow solid (83.5 mg, 49% yield). MS m/z 575(MH+); 1H NMR (500 MHz, CDCl3) δ ppm 1.21–1.31 (m, 3 H) 1.69–1.90 (m, 7 H) 2.53 (m, 1 H) 3.65 (m, 1 H) 3.72 (m, 1 H) 3.92 (s, 3 H) 4.17 (m, 1 H) 4.27 (m, 1 H) 4.32 (s, 2 H) 5.21 (s, 2 H) 6.18 (t, J=6.87 Hz, 1 H) 7.07–7.12 (m, 2 H) 7.21–7.36 (m, 9 H) 7.41 (dd, J=6.71, 2.14 Hz, 1 H) 7.74 (dd, J=8.54, 1.22 Hz 1 H) 7.78 (m, J=8.55 Hz, 1 H) 8.12 (s, 1 H).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at rt overnight
  3. custombefore being quenched by the addition of water
  4. extractionThe resultant mixture was extracted with ethyl acetate (2×20 mL)
  5. washwashed with 1N HCl solution
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was then purified by Prep

Sources & evidence

ORD record
ord-12a9eb092e804f1db38491a85f6cceda
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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