p-Toluenesulfonic acid → methyl 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylate

HRID 2364666Notes

Reaction equation

HRID 2364666 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:12])[C:7](=[O:13])[C@@H:6]([CH2:14][CH3:15])[N:5]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:4]=2[N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:31]([O:33][CH3:34])=[O:32])=[C:26]2[C:30]=1[O:29][CH2:28][CH2:27]2.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CC(C)CC(O)C>[CH:16]1([N:5]2[C:4]3[N:3]=[C:2]([NH:21][C:22]4[CH:23]=[CH:24][C:25]([C:31]([O:33][CH3:34])=[O:32])=[C:26]5[C:30]=4[O:29][CH2:28][CH2:27]5)[N:11]=[CH:10][C:9]=3[N:8]([CH3:12])[C:7](=[O:13])[C@H:6]2[CH2:14][CH3:15])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 24820413(R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-oneHCID 68107686Methyl 7-amino-2,3-dihydrobenzofuran-4-carboxylate

Product 1

HCID 68107956methyl 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylateYield 74.1%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

(7R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-5H-pteridin-6-one 1o (670 mg, 2.30 mmol), methyl 7-amino-2,3-dihydrobenzofuran-4-carboxylate 1g (440 mg, 2.30 mmol) and p-toluenesulfonic acid (700 mg, 3.68 mmol) were dissolved in 25 mL 4-methyl-2-pentanol. The resulting solution was heated to reflux for 6 hours with stirring. The reaction solution was added with 25 mL of saturated sodium bicarbonate solution, extracted with ethyl acetate (50 mL×3). The combined organic phase was washed with water (50 mL×3) and saturated sodium chloride solution (50 mL×3) successively, then dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound methyl 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylate 1p (0.77 g, yield: 74.0%) as a light yellow solid.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 6 hours
  3. extractionextracted with ethyl acetate (50 mL×3)
  4. washThe combined organic phase was washed with water (50 mL×3) and saturated sodium chloride solution (50 mL×3) successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7de742ec94ae46649af527cdc74b64ab
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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