Hydrochloric Acid → HCID 86731017, compound

HRID 1852483Notes

Reaction equation

[C:1]([CH:3]1[CH2:12][CH2:11][C:6]2(OCC[O:7]2)[CH2:5][CH:4]1[N:13]1[CH:17]=[C:16]([C:18]([NH2:20])=[O:19])[C:15]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:14]1)#[N:2].C1COCC1.Cl>CCOC(C)=O>[C:1]([CH:3]1[CH2:12][CH2:11][C:6](=[O:7])[CH2:5][CH:4]1[N:13]1[CH:17]=[C:16]([C:18]([NH2:20])=[O:19])[C:15]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:14]1)#[N:2]

Participants

Conditions

Temperature: 75 °C

Procedure

To a vial containing 1-(8-cyano-1,4-dioxaspiro[4.5]dec-7-yl)-3-(phenylamino)-1H-pyrazole-4-carboxamide (Example #2-4, 37 mg, 0.10 mmol) was added THF (0.38 mL), and 1N aqueous HCl (0.13 mL). The resulting mixture was heated to 75° C. for 5.5 hours. The reaction mixture was allowed to cool to ambient temperature and was diluted with EtOAc. The layers were separated and the organic layer was washed with water, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was dissolved in DMSO and purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and lyophilized to afford the title compound as a 1:1 mixture of cis and trans isomers.

Workup

temperatureto cool to ambient temperature
customThe layers were separated
washthe organic layer was washed with water, saturated aqueous NaHCO3, brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in DMSO
custompurified by reverse-phase preparative HPLC (MeCN/water

Sources & evidence

ORD record: ord-4ba6d07e2f384c2aa01a8484dd432dcd
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962608B2

Reaction notes

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