Aluminium lithium hydride → HCID 136140510, compound

HRID 1594399Notes

Reaction equation

HRID 1594399 reaction equation
[O:1]=[C:2]1[CH2:5][CH:4]([C:6]2[NH:7][N:8]=[C:9]3[C:14]=2[CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][C:11](=[O:21])[NH:10]3)[CH2:3]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:1][CH:2]1[CH2:5][CH:4]([C:6]2[NH:7][N:8]=[C:9]3[C:14]=2[CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][C:11](=[O:21])[NH:10]3)[CH2:3]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 136140508HCID 136140508, compound

Product 1

HCID 136140510HCID 136140510, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 3-(3-oxo-cyclobutyl)-4-phenyl-2,4,5,7-tetrahydro-pyrazolo[3,4-b]pyridin-6-one (0.91 g, 3.23 mmol) in THF (20 mL) at 0° C. (ice water bath) was added slowly down the side of the flask a solution of LAH (6.4 mL, 1 M hexanes). After one hr, the reaction was quenched with H2O, 15% NaOH, H2O (0.24 □L:0.24 □L:0.71 □L) and then diluted with EtOAc. To this slurry was added 5 g of silica gel and this mixture was concentrated and dried under reduced pressure. Purification of this material was accomplished by MPLC using 40 g ISCO column (dry pack condition), eluting with a gradient of 5%, 10%, 20% MeOH/CH2Cl2. The product-containing fractions were collected and concentrated to give the title compound (0.50 g, 55%) as a colorless solid. Rf=0.42 (20% MeOH/CH2Cl2). 400 MHz 1H NMR (DMSO-d6) d 11.90 (s, 1H), 10.29 (s, 1H), 7.28-7.23 (m, 2H), 7.20-7.15 (m, 2H), 7.10-7.06 (m, 1H), 5.04 (d, J=6.2 Hz, 1H), 4.16 (dd, J=7.0,4.1 Hz, 1H), 3.86-3.76 (m, 1H), 2.84 (dd, J=15.7, 7.5 Hz, 1H), 2.52 (dddd, J=10.4, 10.4, 7.5, 7.5 Hz, 1H), 2.50-2.48 (dd, J=masked by DMSO, 4.1 Hz, 1H), 2.29-2.12 (m, 2H), 1.89-1.72 (m, 2H). 100 MHz 13C NMR (DMSO-d6) d 170.0, 149.6, 145.0, 142.2, 129.2, 127.5, 127.2, 101.7, 62.4, 41.4, 34.4, 21.2. LRMS m/z (APCI+) 284 (M+1).

Workup

  1. customthe reaction was quenched with H2O, 15% NaOH, H2O (0.24 □L:0.24 □L:0.71 □L)
  2. additiondiluted with EtOAc
  3. additionTo this slurry was added 5 g of silica gel
  4. concentrationthis mixture was concentrated
  5. customdried under reduced pressure
  6. customPurification of this material
  7. custom40 g ISCO column (dry pack condition)
  8. washeluting with a gradient of 5%, 10%, 20% MeOH/CH2Cl2
  9. customThe product-containing fractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-95412a58b7744190b2cb48c1cf5e5c74
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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