Aluminium lithium hydride → 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)-2-methylpropan-1-ol

HRID 1498434Notes

Reaction equation

HRID 1498434 reaction equation
C([O:3][C:4](=O)[C:5]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:36]=[CH:35][C:17]3[C:18]4[N:22]([CH2:23][CH2:24][O:25][C:16]=3[CH:15]=2)[CH:21]=[C:20]([C:26]2[N:27]([CH:32]([CH3:34])[CH3:33])[N:28]=[C:29]([CH3:31])[N:30]=2)[N:19]=4)[CH2:10][CH2:9]1)([CH3:7])[CH3:6])C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:32]([N:27]1[C:26]([C:20]2[N:19]=[C:18]3[C:17]4[CH:35]=[CH:36][C:14]([CH:11]5[CH2:10][CH2:9][N:8]([C:5]([CH3:7])([CH3:6])[CH2:4][OH:3])[CH2:13][CH2:12]5)=[CH:15][C:16]=4[O:25][CH2:24][CH2:23][N:22]3[CH:21]=2)=[N:30][C:29]([CH3:31])=[N:28]1)([CH3:34])[CH3:33]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 582048822-{4-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionic acid ethyl ester

Product 1

HCID 582049962-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)-2-methylpropan-1-olYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-{4-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionic acid ethyl ester (47 mg, 0.092 mmol) in anhydrous THF (3 mL) was cooled to 0° C. and treated with lithium aluminium hydride (1M solution in THF, 0.3 mL, 0.3 mmol), the mixture stirred and allowed to warm to RT before quenching by the addition of saturated aqueous sodium hydrogen carbonate. The resultant mixture was extracted twice with ethyl acetate, the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to RPHPLC (C18 column, gradient 0 to 60% methanol in water+0.1% formic acid) to give 358 as a white solid (20 mg, 47%). LCMS: RT=2.74 min, [M+H]+=465. 1H NMR 400 MHz (DMSO-d) δ: 8.33 (1 H, d, J=8.28 Hz), 8.26 (1 H, s), 7.87 (1 H, s), 7.05 (1 H, dd, J=8.35, 1.77 Hz), 6.90 (1 H, d, J=1.71 Hz), 5.82-5.81 (1 H, m), 4.49 (4 H, m), 3.38 (2 H, s), 3.21 (2 H, d, J=11.33 Hz), 2.58 (1 H, t, J=11.87 Hz), 2.47 (2 H, d, J=11.47 Hz), 2.26 (3 H, s), 1.85 (2 H, d, J=12.54 Hz), 1.72 (2 H, m), 1.46 (6 H, d, J=6.60 Hz), 1.07 (6 H, s)

Workup

  1. custombefore quenching by the addition of saturated aqueous sodium hydrogen carbonate
  2. extractionThe resultant mixture was extracted twice with ethyl acetate
  3. dry with materialthe combined organic extracts dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a622c7ffb2b04684baa4b8b2fb2b5255
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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