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 2385933Notes

Reaction equation

HRID 2385933 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. 1 H NMR δ (ppm) (DMSO-d6): 8.26 (1 H, d, J=8.17 Hz), 8.06 (1 H, d, J=0.59 Hz), 7.16 (1 H, dd, J=8.23, 1.81 Hz), 7.00 (1 H, d, J=1.76 Hz), 5.83-5.75 (1 H, m), 4.32 (2 H, t, J=5.03 Hz), 4.00 (1H, s), 3.65 (2 H, t, J=6.98 Hz), 3.61-3.51 (1 H, m), 3.39 (2 H, t, J=5.08 Hz), 3.14 (2 H, t, J=6.52 Hz), 2.32 (2 H, s), 1.51 (6 H, d, J=6.59 Hz), 1.03 (6 H, 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-5bfe6a20c0a747a2aa47ff8bc9caf698
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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