Tert-Butyl nitrite → 1-Methoxy-9-trifluoromethyl-5H-6-thia-4,5-diaza-chrysene 6,6-dioxide

HRID 513637Notes

Reaction equation

N[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[S:12]([NH:15][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[CH:23][CH:22]=[C:21]2[O:26][CH3:27])(=[O:14])=[O:13].C(ON=O)(C)(C)C>CC(O)=O.C1COCC1>[CH3:27][O:26][C:21]1[C:20]2[C:25](=[C:16]3[C:17](=[CH:18][CH:19]=2)[C:2]2[C:3](=[CH:4][CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=2)[S:12](=[O:14])(=[O:13])[NH:15]3)[N:24]=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

A solution of 2-amino-N-(4-methoxy-quinolin-8-yl)-4-trifluoromethyl-benzenesulfonamide (Intermediate 196) (454 mg, 1.1 mmol) in AcOH/THF (1:1, 10 ml) was cooled to 0° C. and tert-butylnitrite (235 mg, 2.2 mmol) was added. The reaction was stirred at 0-5° C. for 2 h. The reaction was quenched water (5 ml) and the solvent partially evaporated. The residue was dissolved in EtOAc (150 ml), washed with sat. sodium bicarbonate solution, dried (MgSO4) and concentrated in vacuo. The crude residue was purified by column chromatography with DCM/MeOH (1:0-99:1) gradient elution followed by recrystallisation from iPA/MeCN to give the title compound (45 mg, 11%).

Workup

customThe reaction was quenched water (5 ml)
customthe solvent partially evaporated
dissolutionThe residue was dissolved in EtOAc (150 ml)
washwashed with sat. sodium bicarbonate solution
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe crude residue was purified by column chromatography with DCM/MeOH (1:0-99:1) gradient elution
customfollowed by recrystallisation from iPA/MeCN

Sources & evidence

ORD record: ord-828f27fa6aa940f8a7e1bef58d119239
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102688B2

Reaction notes

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