Azidotrimethylsilane → HCID 178497408, compound

HRID 62423

Reaction equation

HRID 62423 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.C(Cl)Cl>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 78378AzidotrimethylsilaneHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 21226129Dichloromethane methanolHCID 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 condenser). (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/CH2Cl2 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-77cab358e5e0421eaefc27946375a9a0
Source dataset
uspto-grants-2016_09
Patent number
US09446041B2

Linked notes

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