1-Tert-butylpiperazine → HCID 68313121, compound

HRID 1530546Notes

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.[C:30]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)([CH3:33])([CH3:32])[CH3:31]>O1CCOCC1>[C:30]([N:34]1[CH2:39][CH2:38][N:37]([CH:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:12][CH2:13][CH2:14][N:15]4[CH:16]=[C:17]([C:22]5[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[CH:24][N:23]=5)[N:18]=[C:19]4[C:20]=3[CH:21]=2)[CH3:7])[CH2:36][CH2:35]1)([CH3:33])([CH3:32])[CH3:31]

Participants

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 (140 mg, 0.340 mmol) and 1-tert-butylpiperazine (238 mg, 1.70 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 racemic 10-(1-(4-tert-butylpiperazin-1-yl)ethyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine. Further purification and separation of enantiomers was conducted by chiral HPLC (OD-H column, 2% EtOH (0.1% DEA) in n-hexane isocratic) to give a first eluting peak, 26 mg of 149 and a second eluting peak, 27 mg of 150 (34% total yield)

Workup

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

Sources & evidence

ORD record: ord-02dba6875aa64e1186254126fe7f541b
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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