Dimethylformamide → 1-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-3-(2-hydroxy-1-hydroxymethylethyl)urea

HRID 1295432Notes

Reaction equation

HRID 1295432 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]([C@@](O)([C@@H](O)[C@H](O)[C@H](O)CO)C(N)=O)=[CH:16][CH:15]=1.[NH2:33][CH:34]([CH2:37][OH:38])[CH2:35][OH:36].C[N:40]([CH:42]=[O:43])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]=[C:18]([NH:40][C:42]([NH:33][CH:34]([CH2:37][OH:38])[CH2:35][OH:36])=[O:43])[CH:17]=[CH:16][CH:15]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 68294SerinolHCID 69511913[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanamide2×

Product 1

HCID 113847081-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-3-(2-hydroxy-1-hydroxymethylethyl)urea

Procedure

1.02 g (2.0 mmol) of 4-nitrophenyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]carbamate hydrochloride (intermediate 1) were dissolved in 30 ml of abs. DMF and admixed at 0° C. with a solution of 200.5 mg (2.2 mmol) of 2-amino-1,3-propanediol in 25 ml of abs. DMF. The mixture was stirred at room temperature for 3 hours. After standing overnight, the solvent was removed in vacuo and the residue partitioned between ethyl acetate and saturated NaHCO3 solution. The organic phase was removed and the aqueous extracted twice more with ethyl acetate. The combined organic phases were washed with saturated NaCl solution, dried over Na2SO4 and concentrated. Chromatography of the crude product obtained in this way on silica gel (dichloromethane/methanol mixture) afforded 500 mg of the desired urea.

Workup

  1. waitAfter standing overnight
  2. customthe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate and saturated NaHCO3 solution
  4. customThe organic phase was removed
  5. extractionthe aqueous extracted twice more with ethyl acetate
  6. washThe combined organic phases were washed with saturated NaCl solution
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customChromatography of the crude product obtained in this way on silica gel (dichloromethane/methanol mixture)

Sources & evidence

ORD record
ord-c80e5e7e176b4453a237a922b71b4879
Source dataset
uspto-grants-2007_07
Patent number
US07241775B2

Reaction notes

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