Isobutylene oxide → HCID 58204817, compound

HRID 1498355Notes

Reaction equation

HRID 1498355 reaction equation
FC(F)(F)C(O)=O.[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].Cl([O-])(=O)(=O)=O.[Li+].CCN(C(C)C)C(C)C.[O:51]1[C:53]([CH3:55])([CH3:54])[CH2:52]1>C1COCC1.C(Cl)Cl.O>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[C:23]4[CH:26]=[CH:27][C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:52][C:53]([CH3:55])([OH:51])[CH3:54])[CH2:32][CH2:31]5)=[CH:29][C:22]=4[O:21][CH2:20][CH2:19][N:18]3[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9]

Participants

8

Reactant 4

HCID 11208Isobutylene oxideHCID 81531Diisopropylethylamine2×HCID 23665649Lithium perchlorateHCID 670507222-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt

Product 1

HCID 58204817HCID 58204817, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoro acetate (300 mg, 0.61 mmol) in THF (8 mL) was added lithium perchlorate (65 mg, 0.61 mmol) and DIPEA (0.21 mL, 1.21 mmol) followed by 1,2-epoxy-2-methylpropane (0.54 mL, 0.81 mmol) and the mixture stirred at RT for 5 h before the addition of water (2.5 mL). After stirring for a further 18 h then DIPEA (0.16 mL, 0.92 mmol) added and the mixture heated at 45° C. for 5 h then at RT for 72 h. The reaction mixture was diluted with DCM and washed with water before being dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, preconditioned with 25% TEA in DCM, gradient 0 to 5% methanol in DCM) then freeze dried from methanol/water and triturated in petroleum ether to give 292 as a cream solid (92 mg, 34%). LCMS: RT=2.76 min, [M+H]+=451. 1H NMR 400 MHz (DMSO-d ) δ: 8.32 (1 H, d, J=8.28 Hz), 7.90 (2 H, d, J=2.80 Hz), 7.05 (1 H, dd, J=8.35, 1.77 Hz), 6.90 (1 H, d, J=1.70 Hz), 7.27-4.48 (1 H, m), 4.49 (4 H, q, J=5.87 Hz), 4.03 (1 H, s), 3.04 (2 H, d, J=10.80 Hz), 2.46 (1 H, s), 2.23 (4 H, s), 1.70 (4 H, s), 1.48 (6 H, d, J=6.59 Hz), 1.10 (6 H, s)

Workup

  1. waitat RT for 72 h
  2. washwashed with water
  3. dry with materialbefore being dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dry with materialthen freeze dried from methanol/water
  7. customtriturated in petroleum ether

Sources & evidence

ORD record
ord-3e4c29b6e96a49c0b1a83d05f6575f2e
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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