Hydrochloric Acid → [1-({[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)cyclobutyl]methanol

HRID 2189081Notes

Reaction equation

HRID 2189081 reaction equation
[OH-].[Na+].[C:3]1([CH2:9][OH:10])([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4]1.Cl[C:12]1[C:13]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[C:19]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:18][C:14]=2[N:15]=[CH:16][N:17]=1.Cl>C1(C)C=CC=CC=1.COCCOC.O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:28][O:27][C:24]1[CH:23]=[CH:22][C:21]([C:20]2[C:13]3[C:12]([O:8][CH2:7][C:3]4([CH2:9][OH:10])[CH2:6][CH2:5][CH2:4]4)=[N:17][CH:16]=[N:15][C:14]=3[O:18][C:19]=2[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4498243Cyclobutane-1,1-diyldimethanolHCID 580168154-Chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 58280249[1-({[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)cyclobutyl]methanol

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

Add 2.6 ml of an 11.25N sodium hydroxide solution at 70° C. to a solution of 1.72 g (14.85 mmol) of cyclobutane-1,1-diyldimethanol [F. X. Tavares, J. Med. Chem. 2004, 47 (21), 5057-5068] in 20 ml of toluene, 8 ml of 1,2-dimethoxyethane and 8 ml of water. After adding 0.10 g (0.30 mmol) of tetra-n-butylammonium hydrogen sulphate and 1.00 g (2.97 mmol) of 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine, stir the reaction mixture at 70° C. for 17 h. After cooling to room temperature, adjust to pH 7 with concentrated hydrochloric acid. Extract three times with 50 ml of dichloromethane each time. Wash the combined organic extracts with satd. sodium chloride solution, dry over sodium sulphate and filter. Concentrate the filtrate under reduced pressure. Stir the residue in acetonitrile, filter and purify the filtrate by means of preparative RP-HPLC (gradient: water/acetonitrile). 0.30 g (24% of theory) of the desired product are obtained.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionExtract three times with 50 ml of dichloromethane each time
  3. washWash the combined organic extracts with satd
  4. dry with materialsodium chloride solution, dry over sodium sulphate
  5. filtrationfilter
  6. concentrationConcentrate the filtrate under reduced pressure
  7. stirringStir the residue in acetonitrile
  8. filtrationfilter
  9. custompurify the filtrate by means of preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-0770611fae7145bfb51ee65506c9fba9
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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