Cl.[NH2:2][C:3]([NH2:5])=[NH:4].CC([O-])(C)C.[K+].Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[N:30])[CH:24]=3)[CH:21]=2)[C:16]([Cl:31])=[CH:15][N:14]=1>COCCOC.CN1C(=O)CCC1>[Cl:31][C:16]1[C:17]2[C:22](=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[N:30])[CH:24]=3)=[CH:19][CH:18]=2)[C:13]([NH:4][C:3]([NH2:5])=[NH:2])=[N:14][CH:15]=1A stirred suspension of guanidine hydrochloride (3.8 kg, 39.8 mol) and KOtBu (4.28 kg, 38.1 mol) in DME (17.6 L) was heated to reflux under N2 for 1 hour. The gum containing solution was cooled to room temperature, diluted with NMP (8.8 L) and 1,4-dichloro-7-(3-cyanophenyl)isoquinoline (4.4 kg, 14.7 mol) was added as a solid. The mixture was heated at reflux overnight, cooled to room temperature, filtered through a pad of celite and the pad washed with DME (4.4 L). Water (35.2 L) was added to the filtrate. The resultant slurry was stirred for 2 hour and the solid collected by filtration. The solid was washed with water (4.4 L) and dried in vacuo at 50° C. to give (4-chloro-7-(3-cyanophenyl)isoquinolin-1-yl)guanidine (4.55 kg, 14.1 mol, 96%) as a green solid.
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