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

HRID 45679Notes

Reaction equation

HRID 45679 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

6

Reactant 3

HCID 94429TriphosgeneHCID 1112071,4-Dimethyl L-aspartateHCID 99443944-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)aniline2×

Product 1

HCID 46843171(2S)-dimethyl 2-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)succinate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

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 eltued 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

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 1 h at room temperature
  4. stirringThe resulting solution was stirred for 2 h at room temperature
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. 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-87b42122c21a4e61951c079e25c1d5c8
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

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