Isobutylene oxide → 1-{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-2-ol

HRID 1190617Notes

Reaction equation

HRID 1190617 reaction equation
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1.C(N(C(C)C)CC)(C)C.[O:43]1[C:45]([CH3:47])([CH3:46])[CH2:44]1>CO>[CH:29]([N:25]1[C:24]([C:18]2[S:19][C:20]3[CH2:21][CH2:22][O:23][C:14]4[CH:13]=[C:12]([CH:10]5[CH2:11][N:8]([CH2:44][C:45]([CH3:47])([OH:43])[CH3:46])[CH2:9]5)[CH:33]=[CH:32][C:15]=4[C:16]=3[N:17]=2)=[N:28][CH:27]=[N:26]1)([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 11208Isobutylene oxideHCID 81531DiisopropylethylamineHCID 866523168-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 582038081-{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-2-olYield 38.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 (250 mg, 0.52 mmol) in MeOH (3 mL) was added diisopropylethylamine (110 μL, 0.62 mmol) followed by 1,2-epoxy-2-methylpropane (230 μL, 2.6 mmol) and the reaction mixture was stirred at RT for 18 hours. The reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (SiO2, 0-7.5% MeOH in DCM) to give a solid that was recrystallised from heptane to give 421 (87 mg, 38%). LCMS: RT=7.41 min, [M+H]+=440. 1H NMR δ (ppm) (DMSO-d6): 8.26 (1H, d, J=8.17 Hz), 8.06 (1H, d, J=0.59 Hz), 7.16 (1H, dd, J=8.23, 1.81 Hz), 7.00 (1H, d, J=1.76 Hz), 5.83-5.75 (1H, m), 4.32 (2H, t, J=5.03 Hz), 4.00 (1H, s), 3.65 (2H, t, J=6.98 Hz), 3.61-3.51 (1H, m), 3.39 (2H, t, J=5.08 Hz), 3.14 (2H, t, J=6.52 Hz), 2.32 (2H, s), 1.51 (6H, d, J=6.59 Hz), 1.03 (6H, s)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue purified by flash chromatography (SiO2, 0-7.5% MeOH in DCM)
  3. customto give a solid
  4. customthat was recrystallised from heptane

Sources & evidence

ORD record
ord-b088716345424d778ae2ebe26d8a1641
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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