Methanol → HCID 178497408, compound

HRID 1477059Notes

Reaction equation

HRID 1477059 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:16]([O:18][CH3:19])=[O:17])[C:6]2[C:7]([CH3:15])=[CH:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1)#[N:2].[N:20]([Si](C)(C)C)=[N+:21]=[N-:22].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CO>CCOC(C)=O.CC(O)=O>[CH:12]([N:9]1[C:10]2[CH:11]=[C:3]([C:1]3[NH:22][N:21]=[N:20][N:2]=3)[CH:4]=[C:5]([C:16]([O:18][CH3:19])=[O:17])[C:6]=2[C:7]([CH3:15])=[CH:8]1)([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 887MethanolHCID 78378AzidotrimethylsilaneHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 67467281methyl 6-cyano-1-isopropyl-3-methyl-1H-indole-4-carboxylate

Product 1

HCID 178497408HCID 178497408, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred suspension of methyl 6-cyano-1-isopropyl-3-methyl-1H-indole-4-carboxylate (0.50 g, 1.951 mmol) in azidotrimethylsilane (1.0 mL, 7.53 mmol) in a small vial was added tetrabutylammonium fluoride trihydrate (300 mg, 0.951 mmol). The reaction was heated to 85° C. and stirred for 18 hr (attached a small reflux condensor). (The reaction became a semi-solid mass.) The reaction was taken up in EtOAc (75 mL), washed with 1 N HCl (75 mL) (stirred till dissolved). The organic phase was removed, dried (Na2SO4), filtered and concentrated under vacuum. Purification by silica gel chromatography (Analogix, SF40-80 g, 0 to 3% MeOH/CH2C12 with 0.1% HOAc) gave the product methyl 1-isopropyl-3-methyl-6-(1H-tetrazol-5-yl)-1H-indole-4-carboxylate (0.28 g, 0.935 mmol, 48.0% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J=1.3 Hz, 1H), 8.15 (d, J=1.5 Hz, 1H), 7.69 (s, 1H), 4.86 (quin, J=6.6 Hz, 1H), 3.94 (s, 3H), 2.33 (s, 3H), 1.50 (d, J=6.6 Hz, 6H). MS(ES)+m/e 300.3 [M+H]+.

Workup

  1. washwashed with 1 N HCl (75 mL) (stirred till dissolved)
  2. customThe organic phase was removed
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customPurification by silica gel chromatography (Analogix

Sources & evidence

ORD record
ord-86e2a1a6f8f94f1faef1cca1e5b450c5
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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