1,4-Dioxane → HCID 66558839, compound

HRID 1530570Notes

Reaction equation

HRID 1530570 reaction equation
CS(O[CH:6]([C:8]1[CH:21]=[C:20]2[C:11]([O:12][CH2:13][CH2:14][N:15]3[C:19]2=[N:18][C:17]([C:22]2[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[CH:24][N:23]=2)=[CH:16]3)=[CH:10][CH:9]=1)[CH3:7])(=O)=O.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.O1CCOC[CH2:38]1>>[CH:27]([N:26]1[C:22]([C:17]2[N:18]=[C:19]3[C:20]4[CH:21]=[C:8]([CH:6]([N:34]5[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]5)[CH2:7][CH3:38])[CH:9]=[CH:10][C:11]=4[O:12][CH2:13][CH2:14][N:15]3[CH:16]=2)=[N:23][CH:24]=[N:25]1)([CH3:29])[CH3:28]

Participants

4

Reactant 3

HCID 312751,4-DioxaneHCID 531671-MethylpiperazineHCID 86671465HCID 86671465, compound

Product 1

HCID 66558839HCID 66558839, compound

Conditions

Temperature
90 °C

Procedure

A mixture of 1-{4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-13-yl}ethyl methanesulfonate from Example 146 (244 mg, 0.570 mmol) and 1-methylpiperazine (280 mg, 2.80 mmol) in 1,4-dioxane (4 mL) was stirred at 90° C. for 16 h under nitrogen atmosphere. After concentration, the residue was purified by reverse phase Combiflash eluting with a 0-50% gradient of CH3CN in 0.3% NH4HCO3 to give 170. The enantiomers were separated by chiral HPLC (OD-H column, 5% EtOH (0.1% DEA) in n-hexane isocratic) to give: 20 mg of one enantiomer and 16 mg of the other (15% total yield).

Workup

  1. concentrationAfter concentration
  2. customthe residue was purified by reverse phase Combiflash
  3. washeluting with a 0-50% gradient of CH3CN in 0.3% NH4HCO3

Sources & evidence

ORD record
ord-87dd99fbe95140d1beeffaf811380726
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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