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

HRID 1190685Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([N:5]2[CH:9]=[C:8]([C:10]3[CH:32]=[CH:31][C:13]4[C:14]5[N:15]=[C:16]([C:22]6[N:23]([CH:28]([CH3:30])[CH3:29])[N:24]=[C:25]([CH3:27])[N:26]=6)[S:17][C:18]=5[CH2:19][CH2:20][O:21][C:12]=4[CH:11]=3)[CH:7]=[N:6]2)[CH2:2]1.CO.C(N(CC)C(C)C)(C)C.[CH3:44][C:45]1([O:48][CH2:47]1)[CH3:46]>>[CH:28]([N:23]1[C:22]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:12]4[CH:11]=[C:10]([C:8]5[CH:7]=[N:6][N:5]([CH:3]6[CH2:4][N:1]([CH2:44][C:45]([CH3:47])([OH:48])[CH3:46])[CH2:2]6)[CH:9]=5)[CH:32]=[CH:31][C:13]=4[C:14]=3[N:15]=2)=[N:26][C:25]([CH3:27])=[N:24]1)([CH3:29])[CH3:30]

Participants

Reactant 4

HCID 887Methanol

HCID 11208Isobutylene oxide

HCID 81531Diisopropylethylamine

HCID 582038588-(1-Azetidin-3-yl-1H-pyrazol-4-yl)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 582040491-(3-{4-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-azetidin-1-yl)-2-methyl-propan-2-olYield 9%

Procedure

To a slurry of 8-(1-Azetidin-3-yl-1H-pyrazol-4-yl)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (0.232 g, 0.000519 mol) in methanol (3.0 mL, 0.074 mol) was added N,N-Diisopropylethylamine (0.108 mL, 0.000623 mol) then isobutylene oxide (0.330 mL, 0.0037 mol). The reaction was stirred at room temperature overnight. The solvent was removed in vacuo and purified by reverse-phase HPLC to give 480 (24.3 mg) as a colorless solid. MS (ESI+) 520.2. 1H NMR (400 MHz, DMSO) δ 8.45 (s, 1H), 8.31 (d, J=8.3, 1H), 8.01 (s, 1H), 7.47 (dd, J=8.3, 1.8, 1H), 7.35 (d, J=1.8, 1H), 5.86-5.68 (m, 1H), 4.97 (p, J=6.9, 1H), 4.39 (t, J=5.0, 2H), 4.11 (s, 1H), 3.79 (dd, J=8.0, 7.3, 2H), 3.49 (dd, J=8.0, 6.8, 2H), 3.44 (t, J=5.0, 2H), 2.44 (s, 2H), 2.32 (s, 3H), 1.53 (d, J=6.6, 6H), 1.08 (s, 6H).

Workup

customThe solvent was removed in vacuo
custompurified by reverse-phase HPLC

Sources & evidence

ORD record: ord-9bf7227a6500450d99adf0d2c7f8d988
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673952B2

Reaction notes

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