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

HRID 708163Notes

Reaction equation

HRID 708163 reaction equation
C[O:2][C:3](=O)[C:4]([N:7]1[CH2:10][CH: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)[CH2:8]1)([CH3:6])[CH3:5].[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]([CH:9]5[CH2:8][N:7]([C:4]([CH3:6])([CH3:5])[CH2:3][OH:2])[CH2:10]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 582040882-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propionic acid methyl ester

Product 1

HCID 582037262-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propan-1-olYield 104.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propionic acid methyl ester (147 mg, 0.31 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen was treated dropwise with a 1M solution of LiAlH4 in THF (0.47 mL, 0.47 mmol) and the mixture was stirred for 15 minutes then allowed to warm to RT. After 1.5 hours the mixture was cooled to 0° C. and quenched by cautious addition of water. EtOAc was added and the organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was dissolved in DCM (20 mL) and treated with 4N HCl/dioxan (1 mL). The resulting solid was filtered off, washed with ether and dried to give 427 (142 mg, quant.). LCMS: RT=7.54 min, [M+H]+=440. 1H NMR δ (ppm) (DMSO-d6): 10.61 (1H, s), 8.32 (1H, d, J=8.21 Hz), 8.07 (1H, s), 7.22-7.16 (1H, m), 7.06 (1H, d, J=1.80 Hz), 5.81-5.72 (1H, m), 4.55 (1H, td, J=10.55, 4.79 Hz), 4.38-4.26 (3H, m), 4.16-3.92 (3H, m), 3.46-3.37 (5H, m), 1.53-1.48 (6H, m), 1.27-1.14 (6H, m)

Workup

  1. temperatureAfter 1.5 hours the mixture was cooled to 0° C.
  2. customquenched by cautious addition of water
  3. additionEtOAc was added
  4. washthe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resultant residue was dissolved in DCM (20 mL)
  8. additiontreated with 4N HCl/dioxan (1 mL)
  9. filtrationThe resulting solid was filtered off
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-3acf96fcc2144b94b0994d54bb57a7b0
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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