Potassium bis(trimethylsilyl)amide → Ethyl 1-((1H-indol-3-yl)methyl)-3-isopropyl-1H-pyrazole-5-carboxylate

HRID 1409985Notes

Reaction equation

HRID 1409985 reaction equation
[CH:1]([C:4]1[CH:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[NH:6][N:5]=1)([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(O[CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[N:36](C(=O)C2C=CC=CC=2)[CH:35]=1)(=O)C1C=CC=CC=1>>[NH:36]1[C:37]2[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:34]([CH2:33][N:6]2[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:8][C:4]([CH:1]([CH3:3])[CH3:2])=[N:5]2)=[CH:35]1

Participants

4

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 6422484Ethyl 5-(propan-2-yl)-1H-pyrazole-3-carboxylateHCID 90411032HCID 90411032, compound

Product 1

HCID 86267748Ethyl 1-((1H-indol-3-yl)methyl)-3-isopropyl-1H-pyrazole-5-carboxylate

Procedure

To an oven dried flask cooled under argon equipped with a stir bar was added ethyl 3-isopropyl-1H-pyrazole-5-carboxylate (0.044 grams, 0.24 mmol, 0.1 in anhydrous 1,4 dioxane). While stirring at room temperature KHMDS (0.3 mL, 0.261 mmol, 0.87 M in toluene) was added. After stirring for 45 minutes, a solution of (1-benzoyl-1H-indol-3-yl)methyl benzoate (0.02 grams, 0.056 mmol, in 1.0 mL of anhydrous 1,4 dioxane) was added and the reaction mixture stirred over night. The next day, the reaction was quenched with 0.1M HCl and the organic material extracted with ethyl acetate. The aqueous solution was then salted out using sodium chloride and washed twice with ethyl acetate. The combined organic material was then dried with sodium sulfate, filtered, and concentrated. Purification using a Teledyne ISCO chromatography on silica gel (hexanes/ethyl acetate gradient) followed by a Teledyne ISCO chromatography using C18 reverse phase (water with 0.1% formic acid, acetonitrile gradient) afforded the desired compound. Yield, 63%. 1H NMR δ 8.29 (bs, 1H), 7.58 (d, 1H), 7.36 (d, 1H), 7.20 (t, 1H), 7.11 (t, 1H), 6.96 (s, 1H), 6.62 (s, 1H), 5.58 (s, 2H), 4.41 (q, 2H), 3.03 (m, 1H), 1.39 (t, 3H), 1.16 (d, 6H). Calculated mass for C18H21N3O2, 311.16. Observed 334.1 (M+1).

Workup

  1. customTo an oven dried flask
  2. temperaturecooled under argon
  3. customequipped with a stir bar
  4. additionwas added
  5. stirringthe reaction mixture stirred over night
  6. customThe next day, the reaction was quenched with 0.1M HCl
  7. extractionthe organic material extracted with ethyl acetate
  8. washwashed twice with ethyl acetate
  9. dry with materialThe combined organic material was then dried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification

Sources & evidence

ORD record
ord-e29a93165d85492fbd88fc6ecf5c7310
Source dataset
uspto-grants-2014_12
Patent number
US08921401B2

Reaction notes

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