Tetrahydrofuran → HCID 22638704, compound

HRID 2416277Notes

Reaction equation

HRID 2416277 reaction equation
C([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]#[N:19])[CH:16]=2)[N:11]([S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:22])=[O:21])[N:10]=1)=O)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:35]1COCC1>>[OH:3][CH2:4][CH:6]1[CH2:8][CH:7]1[C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]#[N:19])[CH:16]=2)[N:11]([S:20]([C:23]2[CH:24]=[CH:25][C:26]([CH3:35])=[CH:27][CH:28]=2)(=[O:21])=[O:22])[N:10]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 67551233HCID 67551233, compound

Product 1

HCID 22638704HCID 22638704, compoundYield 58%

Conditions

Temperature
-40 °C

Procedure

2-(1-Benzenesulfonyl-5-cyano-1H-indazol-3-yl)-cyclopropanecarboxylic acid ethyl ester (1.12 g, 2.74 mmol) was dissolved in 30 mL anhydrous THF under N2 and cooled to −40° C. LAH (0.83 g, 22 mmol) was added portionwise over a 15 min. period. The reaction was stirred for 5 h at −40° C., then quenched with 50 mL ethyl acetate, followed by 10 mL water. After stirring at room temperature for 30 min, 50 mL saturated tartrate solution was added and stirred for 30 min. The precipitate was removed by filtration and washed with ethyl acetate. The precipitate was washed with more ethyl acetate, and the organic layer was washed with brine and dried over Na2SO4. Flash chromatography on silica gel using ethyl acetate/hexane (25-50%) as the eluent gave 3-(2-hydroxymethyl-cyclopropyl)-1-(toluene-4-sulfonyl)-1H-indazole-5-carbonitrile (580 mg, 58%). 1H NMR (500 MHz, CDCl3) 8.26 (1H, d, J=8.85 Hz), 8.08 (1H, s), 7.83 (2H, d, J=8.24 Hz), 7.74 (1H, dd, J=8.85, 1.22 Hz), 7.27 (2H, d, J=8.24 Hz), 3.78 (1H, dd, J=11.29, 6.10 Hz), 3.61 (1H, dd, 11.29, 6.71 Hz), 2.38 (3H, s), 2.10 (1H, p, J=4.88 Hz), 1.82 (1H, m), 1.39 (1H, dt, J=8.55, 4.88 Hz), 1.11 (1H, dt, J=8.55, 4.88 Hz). MS m/e 366.15 (M−H)−. Anal. calcd. for C19H17N3O3S: C, 62.11; H, 4.66; N, 11.43. Found: C, 62.16; H, 4.76; N, 11.19.

Workup

  1. customquenched with 50 mL ethyl acetate
  2. stirringAfter stirring at room temperature for 30 min
  3. addition50 mL saturated tartrate solution was added
  4. stirringstirred for 30 min
  5. customThe precipitate was removed by filtration
  6. washwashed with ethyl acetate
  7. washThe precipitate was washed with more ethyl acetate
  8. washthe organic layer was washed with brine
  9. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-5d69a17b68e04f3181c6811c32d7ad18
Source dataset
uspto-grants-2004_11
Patent number
US06822100B2

Reaction notes

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