Isobutylene oxide → HCID 58204542, compound

HRID 1629203Notes

Reaction equation

HRID 1629203 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 L, 0.41 mmol) in THF (3 mL) was treated with 2,2-dimethyl-oxirane (183 L, 2.06 mmol) and then water (150 L). 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, 1 H); 8.28 (s, 1 H); 7.85 (td, J=8.76, 5.90 Hz, 1 H); 7.61 (ddd, J=10.27, 8.88, 2.78 Hz, 1 H); 7.36-7.30 (m, 1 H); 7.22 (d, J=2.31 Hz, 1 H); 7.08 (dd, J=8.38, 2.35 Hz, 1 H); 6.89 (d, J=8.34 Hz, 1 H); 4.21 (t, J=5.02 Hz, 2 H); 4.06 (s, 1 H); 3.12-3.02 (m, 4 H); 2.31-2.19 (m, 5 H); 1.60-1.48 (m, 4 H); 1.15 (s, 6 H). 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-542143f6e6b14d80830c24cfa964e366
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

Loading…