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-9-yl]-azetidin-1-yl}-2-methyl-propan-2-ol

HRID 708127Notes

Reaction equation

HRID 708127 reaction equation
Cl([O-])(=O)(=O)=O.[Li+].[O:7]1[C:9]([CH3:11])([CH3:10])[CH2:8]1.[NH:12]1[CH2:15][CH:14]([C:16]2[CH:17]=[CH:18][C:19]3[O:28][CH2:27][CH2:26][C:25]4[S:24][C:23]([C:29]5[N:30]([CH:34]([CH3:36])[CH3:35])[N:31]=[CH:32][N:33]=5)=[N:22][C:21]=4[C:20]=3[CH:37]=2)[CH2:13]1>C1COCC1>[CH:34]([N:30]1[C:29]([C:23]2[S:24][C:25]3[CH2:26][CH2:27][O:28][C:19]4[CH:18]=[CH:17][C:16]([CH:14]5[CH2:13][N:12]([CH2:8][C:9]([CH3:11])([OH:7])[CH3:10])[CH2:15]5)=[CH:37][C:20]=4[C:21]=3[N:22]=2)=[N:33][CH:32]=[N:31]1)([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 11208Isobutylene oxideHCID 23665649Lithium perchlorateHCID 670505299-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

Product 1

HCID 513550441-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-9-yl]-azetidin-1-yl}-2-methyl-propan-2-olYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium perchlorate (52 mg, 0.49 mmol) was added to THF (5 mL) followed by 1,2-epoxy-2-methylpropane (0.43 mL, 4.9 mmol) and the mixture was stirred for 10-15 minutes giving a clear solution. 9-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 (0.18 g, 0.49 mmol) was added and the reaction mixture was stirred for 72 hours then concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-10% MeOH in EtOAc) and the resulting solid extracted several times with ether. The ether extracts were concentrated in vacuo to give 377 (77 mg, 97%). LCMS: RT=7.45 min, [M+H]+=440. 1H NMR δ (ppm) (CDCl3): 8.28 (1H, d, J=2.34 Hz), 7.90 (1H, s), 7.16 (1H, dd, J=8.29, 2.35 Hz), 7.02 (1H, d, J=8.27 Hz), 5.93-5.83 (1H, m), 4.40-4.34 (2H, m), 4.04-3.95 (2H, m), 3.89-3.79 (1H, m), 3.46-3.36 (4H, m), 2.55 (2H, s), 1.63 (6H, d, J=6.64 Hz), 1.15 (6H, s). 1 Exchangeable proton not seen

Workup

  1. customgiving a clear solution
  2. stirringthe reaction mixture was stirred for 72 hours
  3. concentrationthen concentrated in vacuo
  4. customThe resultant residue was purified by flash chromatography (SiO2, 0-10% MeOH in EtOAc)
  5. extractionthe resulting solid extracted several times with ether
  6. concentrationThe ether extracts were concentrated in vacuo

Sources & evidence

ORD record
ord-bb953455eb3a49b287f389aabcfbed59
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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