Sodium hydride → HCID 69150042, compound

HRID 720446Notes

Reaction equation

HRID 720446 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][NH:11][C:10](=[O:15])[C:9]=2[N:8]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[N:7]=1)=[O:5])[CH3:2].[H-].[Na+].[C:26]([O:29][CH2:30][CH2:31][CH2:32][CH2:33]Br)(=[O:28])[CH3:27]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][N:11]([CH2:33][CH2:32][CH2:31][CH2:30][O:29][C:26](=[O:28])[CH3:27])[C:10](=[O:15])[C:9]=2[N:8]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 784911-Butanol, 4-bromo-, 1-acetateHCID 22240468Ethyl 1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo(3,4-c)pyridine-3-carboxylate

Product 1

HCID 69150042HCID 69150042, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Part A: 1-(4-Methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (1.0 g, 3.17 mmol) was dissolved in N,N-dimethylformamide (40 mL) and cooled to 0° C. Sodium hydride (60%, 0.317 g, 7.93 mmol) was added followed by 4-bromobutyl acetate (0.918 mL, 6.34 mmol). The reaction was stirred at rt overnight, quenched with 1N hydrochloric acid (200 mL), extracted with ethyl acetate (3×250 mL), washed with water (2×200 mL), washed with brine (1×200 mL), dried over MgSO4, concentrated, and purified by flash chromatography using 0–100% ethyl acetate/hexanes gradient as the eluent to afford 6-(4-acetoxy-butyl)-1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (0.490 g, 36%). The ester (0.490 g, 0.114 mmol) was dissolved in 5% NH3/ethylene glycol (6 mL) in a pressure tube, heated at 80° C. for 2 hr, cooled, quenched with water (100 mL), extracted with ethyl acetate (3×100 mL), washed with brine (1×100 mL), dried over MgSO4, concentrated, and purified by flash chromatography using 0–100% ethyl acetate gradient and 0–100% methanol/ethyl acetate gradient as the eluents to afford 0.295 g (72%): 1H NMR (CHCl3) δ 7.45 (d, j=8.8 Hz, 2H), 6.97 (d, j=9.1 Hz, 2H), 6.83 (s, 3H), 5.49 (s, 3H), 3.84 (s, 3H), 3.66 (t, j=6.2 Hz, 2H), 3.51 (t, j=7.3 Hz, 2H), 3.23 (t, j=6.8 Hz, 2H), 1.72–1.55 (m, 4H) ppm; Mass Spec 357.3(M−H)−.

Workup

  1. customquenched with 1N hydrochloric acid (200 mL)
  2. extractionextracted with ethyl acetate (3×250 mL)
  3. washwashed with water (2×200 mL)
  4. washwashed with brine (1×200 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-bc0562a135ec4eea8341e8732f0a9799
Source dataset
uspto-grants-2006_11
Patent number
US07135469B2

Reaction notes

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