Toluene → HCID 78321448, compound

HRID 930315Notes

Reaction equation

[NH2:1][C:2]1[O:3][C@H:4]([C:28]([F:31])([F:30])[F:29])[CH2:5][C@:6]([C:10]2[CH:11]=[C:12]([NH:17][C:18](=O)[C:19]3[C:24]([CH3:25])=[CH:23][C:22]([Cl:26])=[CH:21][N:20]=3)[CH:13]=[CH:14][C:15]=2[F:16])([CH2:8][F:9])[N:7]=1.C1(C)C=CC=CC=1.COC1C=CC(P2(=S)SP(C3C=CC(OC)=CC=3)(=S)[S:48]2)=CC=1>CCOC(C)=O>[NH2:1][C:2]1[O:3][C@H:4]([C:28]([F:31])([F:30])[F:29])[CH2:5][C@:6]([C:10]2[CH:11]=[C:12]([NH:17][C:18]([C:19]3[C:24]([CH3:25])=[CH:23][C:22]([Cl:26])=[CH:21][N:20]=3)=[S:48])[CH:13]=[CH:14][C:15]=2[F:16])([CH2:8][F:9])[N:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A sealable vial was charged with N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloro-3-methylpicolinamide (Example 4, 0.068 g, 0.147 mmol) and toluene (1 mL). 2,4-Bis(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane (0.059 g, 0.147 mmol) was added and the reaction mixture was heated to 120° C. overnight. Upon cooling to room temperature, the reaction mixture was taken up in EtOAc (75 mL). The organic layer was washed with aqueous saturated NaHCO3 and with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified through silica gel (gradient 30%-50% EtOAc-hexane) affording the title compound as a yellow solid (8.4 mg, 0.018 mmol, 12%). MS m/z=479 [M+H]+. Calculated for C19H16ClF5N4OS: 478.

Workup

temperatureUpon cooling to room temperature
washThe organic layer was washed with aqueous saturated NaHCO3 and with brine
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure
customThe residue was purified through silica gel (gradient 30%-50% EtOAc-hexane)

Sources & evidence

ORD record: ord-09be41b37b304c65a73a5683d181a40f
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296734B2

Reaction notes

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