Acetone → tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-(methoxymethyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate

HRID 1819311Notes

Reaction equation

HRID 1819311 reaction equation
CI.[Cl:3][C:4]1[CH:41]=[CH:40][CH:39]=[CH:38][C:5]=1[CH2:6][N:7]1[C:15]2[C:14](=[O:16])[N:13]([CH3:17])[C:12](=[O:18])[N:11]([CH3:19])[C:10]=2[C:9]([CH2:20]N(C)C)=[C:8]1[N:24]1[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]1.C[C:43](C)=[O:44]>>[Cl:3][C:4]1[CH:41]=[CH:40][CH:39]=[CH:38][C:5]=1[CH2:6][N:7]1[C:15]2[C:14](=[O:16])[N:13]([CH3:17])[C:12](=[O:18])[N:11]([CH3:19])[C:10]=2[C:9]([CH2:20][O:44][CH3:43])=[C:8]1[N:24]1[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:25]1

Participants

4

Reactant 3

HCID 180AcetoneHCID 6328Methyl iodideHCID 57886917tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-[(dimethylamino)methyl]-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate

Product 1

HCID 57886928tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-(methoxymethyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate

Procedure

Methyl iodide (25 μl) was added to a solution of tert-butyl {(3R)-1-[5-(2-chlorobenzyl)-7-[(dimethylamino)methyl]-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate (112 mg) in acetone (5 ml), and the resulting mixture was stirred overnight in a sealed tube at room temperature. The reaction solution was concentrated under reduced pressure, and to a solution of the resulting residue in methanol (2 ml) was added 28% methanol methoxide (2 ml), followed by stirring with heating at 60° C. for 4 hours. The methanol was distilled off under reduced pressure and the residue was adjusted to pH 2 with an aqueous potassium hydrogensulfate solution and extracted with ethyl acetate (100 ml). The organic layer was washed with a 10% aqueous potassium hydrogensulfate solution and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a thin-layer silica gel column chromatography (hexane/ethyl acetate=1/5) to obtain the title compound (26 mg).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionto a solution of the resulting residue in methanol (2 ml) was added 28% methanol methoxide (2 ml)
  3. stirringby stirring
  4. temperaturewith heating at 60° C. for 4 hours
  5. distillationThe methanol was distilled off under reduced pressure
  6. extractionextracted with ethyl acetate (100 ml)
  7. washThe organic layer was washed with a 10% aqueous potassium hydrogensulfate solution
  8. dry with materiala saturated aqueous sodium chloride solution, dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe resulting residue was purified by a thin-layer silica gel column chromatography (hexane/ethyl acetate=1/5)

Sources & evidence

ORD record
ord-da747980d0374601a443f05d1225355d
Source dataset
uspto-grants-2009_10
Patent number
US07601728B2

Reaction notes

Loading…