[CH3:1][C:2]1([CH3:20])[C:7]2[CH:8]=[C:9]([C:12]3[NH:16][C:15]([C:17]#[N:18])=[CH:14][CH:13]=3)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=O)[O:3]1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:30])=CC=1.COCCOC>C(#N)C>[CH3:1][C:2]1([CH3:20])[C:7]2[CH:8]=[C:9]([C:12]3[NH:16][C:15]([C:17]#[N:18])=[CH:14][CH:13]=3)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=[S:30])[O:3]15-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile (14.5 kg), Lawesson's Reagent (12.1 kg, 1.16 eq.), DME (215 kg), and acetonitrile (8.96 kg) were combined and heated to reflux for at least 4 hours at less than 16 hours to form unpurified 5-(4,4-dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile. The mixture was cooled to 18 to 28° C., quenched with water (276 kg), cooled to 10 to 20° C., stirred for at least 30 minutes, and the resulting slurry collected via filtration.
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