Aluminium lithium hydride → 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]pyrazol-1-yl}-ethanol

HRID 2385655Notes

Reaction equation

HRID 2385655 reaction equation
C([O:3][C:4](=O)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[CH:32]=[CH:31][C:14]3[C:15]4[N:16]=[C:17]([C:23]5[N:24]([CH:28]([CH3:30])[CH3:29])[N:25]=[CH:26][N:27]=5)[S:18][C:19]=4[CH2:20][CH2:21][O:22][C:13]=3[CH:12]=2)[CH:8]=[N:7]1)C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH:28]([N:24]1[C:23]([C:17]2[S:18][C:19]3[CH2:20][CH2:21][O:22][C:13]4[CH:12]=[C:11]([C:9]5[CH:8]=[N:7][N:6]([CH2:5][CH2:4][OH:3])[CH:10]=5)[CH:32]=[CH:31][C:14]=4[C:15]=3[N:16]=2)=[N:27][CH:26]=[N:25]1)([CH3:30])[CH3:29]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 58203911{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-acetic acid ethyl ester

Product 1

HCID 568325102-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]pyrazol-1-yl}-ethanolYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of {4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-acetic acid ethyl ester in THF (200 mL) was cooled to 0° C. and treated dropwise with a solution of 1M LiAlH4 (in THF, 23 mL, 23 mmol, 2.5 eq). After 1 h, LCMS indicated consumption of starting material. A solution of saturated sodium sulfate was added slowly until H2 evolution ceased. ˜30 g of solid magnesium sulfate was added and the whole was stirred for 20 min. Filtration over celite (EtOAc and DCM) follwed by concentration of the filtrant gave a crude residue that was purified by reverse-phase HPLC to give 1.4 g of 105 (43%). LCMS: 423.1. 1HNMR (400 MHz, DMSO) δ 8.32 (d, J=8.3 Hz, 1H), 8.22 (s, 1H), 8.10 (s, 1H), 7.95 (s, 1H), 7.43 (dd, J=8.3, 1.6 Hz, 1H), 7.30 (d, J=1.6 Hz, 1H), 5.84 (dt, J=13.2, 6.6 Hz, 1H), 4.91 (t, J=5.3 Hz, 1H), 4.39 (t, J=4.9 Hz, 2H), 4.16 (t, J=5.6 Hz, 2H), 3.77 (q, J=5.5 Hz, 2H), 3.44 (t, J=4.9 Hz, 2H), 1.56 (d, J=6.6 Hz, 6H).

Workup

  1. customconsumption of starting material
  2. additionA solution of saturated sodium sulfate was added slowly until H2 evolution
  3. addition˜30 g of solid magnesium sulfate was added
  4. filtrationFiltration over celite (EtOAc and DCM)
  5. customgave a crude residue that
  6. customwas purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-2eadd173fa9649e9beccde504036b86d
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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