Aluminium lithium hydride → HCID 66558924, compound

HRID 1530659Notes

Reaction equation

HRID 1530659 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([O:23][C:24]5([C:27]([N:29]6[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]6)=O)[CH2:26][CH2:25]5)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:36])=[N:5]1)([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[CH:20][C:21]([O:23][C:24]5([CH2:27][N:29]6[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]6)[CH2:25][CH2:26]5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][C:6]([CH3:36])=[N:5]1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68312918HCID 68312918, compound

Product 1

HCID 66558924HCID 66558924, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of {1-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]cyclopropyl}-(4-methylpiperazin-1-yl)methanone from Example 50 (90 mg, 0.18 mmol) in THF (5 mL) was added LiAlH4 (1.0M in THF, 0.18 mL) and the mixture was stirred at 0° C. for 2 h. The reaction mixture was quenched by addition of 1N NaOH and then was partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The resulting residue was purified by HPLC (Phenomenex Gemini 5 μm C18 on a 25 min gradient 0-60% 0.1% HCO2H in acetonitrile/water) affording 259 (41 mg, 48%). LCMS: RT 2.73 min [M+H]+ 478.1. 1H NMR (DMSO, 400 MHz): δ 8.30 (1H, d, J=8.96 Hz), 8.18 (1H, s), 7.82 (1H, s), 6.82 (1H, dd, J=8.97, 2.49 Hz), 6.63 (1H, d, J=2.47 Hz), 5.89-5.76 (1H, m), 4.48 (4H, s), 2.69 (2H, s), 2.52-2.41 (3H, m), 2.38-2.21 (7H, s), 2.15 (3H, s), 1.45 (6H, d, J=6.60 Hz), 0.96-0.84 (4H, m)

Workup

  1. customThe reaction mixture was quenched by addition of 1N NaOH
  2. customwas partitioned between water and EtOAc
  3. extractionThe aqueous phase was extracted with EtOAc (×3)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by HPLC (Phenomenex Gemini 5 μm C18 on a 25 min gradient 0-60% 0.1% HCO2H in acetonitrile/water)

Sources & evidence

ORD record
ord-79f9a53a6ce4447795c18dfd6a92c30e
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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