Triphosgene → (2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate

HRID 870170

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1.[C:21](=O)(OC(Cl)(Cl)Cl)[O:22]C(Cl)(Cl)Cl.[NH2:33][C@@H:34]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:35]([O:37][CH3:38])=[O:36]>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:22])[NH:33][C@@H:34]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:35]([O:37][CH3:38])=[O:36])=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenamine (intermediate 30.7) (200 mg, 0.65 mmol, 1.00 equiv) in dichloromethane (10 mL), triethylamine (1.2 mL). This was followed by the addition of bis(trichloromethyl) carbonate (200 mg, 0.67 mmol, 1.03 equiv) slowly with stirring at 0-5° C. The resulting solution was stirred for 1 h at room temperature. To this was added triethylamine (1 mL) followed by (S)-dimethyl 2-aminosuccinate (200 mg, 1.24 mmol, 1.91 equiv) in several batches. The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum and the residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:10-1:5). This resulted in 50 mg (15%) of (2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate as yellow oil.

Workup

customInto a 50-mL 3-necked round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
stirringThe resulting solution was stirred for 1 h at room temperature
stirringThe resulting solution was stirred for 2 h at room temperature
concentrationThe resulting mixture was concentrated under vacuum
washeluted with ethyl acetate/petroleum ether (1:10-1:5)
customThis resulted in 50 mg (15%) of (2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate as yellow oil

Sources & evidence

ORD record: ord-99e7b88b008a43df8570b359bac278c4
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969377B2

Linked notes

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