2,2-Dimethyl-1,3-dioxane-4,6-dione → 1-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)-3-(3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl)urea

HRID 45685Notes

Reaction equation

HRID 45685 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]([NH:20][C:21](=[O:28])[NH:22][CH2:23][CH2:24][C:25](O)=[O:26])=[CH:16][CH:15]=1.Cl.CN(C)CCCN=C=NCC.[CH3:41][C:42]1([CH3:50])[O:47][C:46](=[O:48])[CH2:45][C:44](=[O:49])[O:43]1>ClCCl.CN(C)C1C=CN=CC=1>[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:15]=[CH:16][C:17]([NH:20][C:21]([NH:22][CH2:23][CH2:24][C:25]([CH:45]2[C:46](=[O:48])[O:47][C:42]([CH3:50])([CH3:41])[O:43][C:44]2=[O:49])=[O:26])=[O:28])=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 46843242HCID 46843242, compound

Product 1

HCID 674579011-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)-3-(3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl)urea

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-(3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)ureido)propanoic acid (200 mg, 0.47 mmol, 1.00 equiv) in dichloromethane (20 mL), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (136 mg, 0.71 mmol, 1.50 equiv) and 4-dimethylaminopyridine (115 mg, 0.94 mmol, 1.99 equiv). This was followed by the addition of a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (102 mg, 0.71 mmol, 1.49 equiv) in dichloromethane (2 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 3 h at room temperature. The resulting mixture was washed with KHSO4 (2×10 mL). The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 240 mg (92%) of 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)-3-(3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl)urea as a yellow solid.

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 3 h at room temperature
  4. washThe resulting mixture was washed with KHSO4 (2×10 mL)
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThis resulted in 240 mg (92%) of 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)-3-(3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl)urea as a yellow solid

Sources & evidence

ORD record
ord-0b988369d5f040cea306cafd1ca41a8f
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

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