Methyl iodide → (+/-)-tert-Butyl-4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-methoxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174080Notes

Reaction equation

HRID 2174080 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:14]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([CH3:25])=[C:19]4[C:15]=3[CH:16]=[CH:17][N:18]4[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([OH:13])[CH3:12])=[N:8][C:7]=2[CH:33]=1)#[N:2].[CH3:34]I.[H-].[Na+]>CN(C=O)C>[C:29]([O:28][C:26]([N:18]1[C:19]2[C:15](=[C:14]([C:11]([C:9]3[O:10][C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:33][C:7]=4[N:8]=3)([O:13][CH3:34])[CH3:12])[C:22]([O:23][CH3:24])=[CH:21][C:20]=2[CH3:25])[CH:16]=[CH:17]1)=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86701712tert-butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701714(+/-)-tert-Butyl-4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-methoxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (250 mg, 0.559 mmol) in DMF (5.7 mL) at 0° C. was added successively MeI (0.105 mL, 1.676 mmol) and NaH (60% in mineral, 33.5 mg, 0.838 mmol). The reaction mixture was stirred at 0° C. for 1.5 h. The reaction mixture was quenched with 4 mL of saturated aq. solution of ammonium chloride and diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-30% EtOAc:heptanes) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (dd, J=1.52, 0.63 Hz, 1H) 7.79-7.97 (m, 2H) 7.63 (d, J=3.79 Hz, 1H) 7.05 (d, J=3.79 Hz, 1H) 6.83 (s, 1H) 3.23 (s, 3H) 3.17 (s, 3H) 1.81-2.08 (m, 3H) 1.60 (s, 9H).

Workup

  1. customThe reaction mixture was quenched with 4 mL of saturated aq. solution of ammonium chloride
  2. additiondiluted with water and EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (0-30% EtOAc:heptanes)

Sources & evidence

ORD record
ord-ea928dca8d3345f599f048648cfb3bb8
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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