Isobutylene oxide → HCID 58204542, compound

HRID 886179Notes

Reaction equation

HRID 886179 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[C:14]([N:15]2[N:24]=[C:23]3[C:17]([CH2:18][CH2:19][O:20][C:21]4[CH:28]=[CH:27][C:26]([CH:29]5[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]5)=[CH:25][C:22]=43)=[CH:16]2)=[N:13][CH:12]=[N:11]1.Cl([O-])(=O)(=O)=O.[Li+].CCN(C(C)C)C(C)C.[CH3:50][C:51]1([CH3:54])[CH2:53][O:52]1>C1COCC1.O>[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[C:14]([N:15]2[N:24]=[C:23]3[C:17]([CH2:18][CH2:19][O:20][C:21]4[CH:28]=[CH:27][C:26]([CH:29]5[CH2:34][CH2:33][N:32]([CH2:50][C:51]([CH3:54])([OH:52])[CH3:53])[CH2:31][CH2:30]5)=[CH:25][C:22]=43)=[CH:16]2)=[N:13][CH:12]=[N:11]1

Participants

7

Reactant 4

HCID 11208Isobutylene oxideHCID 81531DiisopropylethylamineHCID 23665649Lithium perchlorateHCID 67050669HCID 67050669, compound

Product 1

HCID 58204542HCID 58204542, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperidin-4-yl-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene hydrochloride (100 mg, 0.21 mmol), lithium perchlorate (22 mg, 0.21 mmol) and DIPEA (72 μL, 0.41 mmol) in THF (3 mL) was treated with 2,2-dimethyl-oxirane (183 μL, 2.06 mmol) and then water (150 μL). The reaction mixture was stirred at RT for 18 h before being concentrated in vacuo. The resultant residue was partitioned between DCM and water, the organic layer separated and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 40 to 100% ethyl acetate in cyclohexane) followed by trituration in a mixture MeOH and water to give 177 as a white solid (58 mg, 54%). 1H NMR (400 MHz, DMSO-d): δ 8.44 (s, 1H); 8.28 (s, 1H); 7.85 (td, J=8.76, 5.90 Hz, 1H); 7.61 (ddd, J=10.27, 8.88, 2.78 Hz, 1H); 7.36-7.30 (m, 1H); 7.22 (d, J=2.31 Hz, 1H); 7.08 (dd, J=8.38, 2.35 Hz, 1H); 6.89 (d, J=8.34 Hz, 1H); 4.21 (t, J=5.02 Hz, 2H); 4.06 (s, 1H); 3.12-3.02 (m, 4H); 2.31-2.19 (m, 5H); 1.60-1.48 (m, 4H); 1.15 (s, 6H). LCMS: RT=7.75 min, M+H+=521

Workup

  1. concentrationbefore being concentrated in vacuo
  2. customThe resultant residue was partitioned between DCM and water
  3. customthe organic layer separated
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26b52824816b43b9b880451b79bccf75
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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