p-Toluenesulfonic acid monohydrate → HCID 68107615, compound

HRID 2364728Notes

Reaction equation

HRID 2364728 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])=[C:6]2[C:10]=1[O:9][CH:8]([CH2:11][N:12]([CH3:14])[CH3:13])[CH2:7]2.Cl[C:26]1[N:35]=[CH:34][C:33]2[N:32]([CH3:36])[C:31](=[O:37])[C@@H:30]([CH2:38][CH3:39])[N:29]([CH:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)[C:28]=2[N:27]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C>[CH:40]1([N:29]2[C:28]3[N:27]=[C:26]([NH:1][C:2]4[CH:3]=[CH:4][C:5]([C:15]([O:17][CH2:18][C:19]5[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=5)=[O:16])=[C:6]5[C:10]=4[O:9][CH:8]([CH2:11][N:12]([CH3:14])[CH3:13])[CH2:7]5)[N:35]=[CH:34][C:33]=3[N:32]([CH3:36])[C:31](=[O:37])[C@H:30]2[CH2:38][CH3:39])[CH2:41][CH2:42][CH2:43][CH2:44]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 24820413(R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-oneHCID 68107386HCID 68107386, compound

Product 1

HCID 68107615HCID 68107615, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

Benzyl 7-amino-2-(dimethylaminomethyl)-2,3-dihydrobenzofuran-4-carboxylate 29g (212 mg, 0.65 mmol) was dissolved in 20 mL of 4-methyl-2-pentanol followed by the addition of (7R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one 1o (230 mg, 0.78 mmol) and p-toluenesulfonic acid monohydrate (198 mg, 1.04 mmol). The reaction solution was heated to reflux for 3 hours with stirring and concentrated under reduced pressure. The resulting residue was added with 30 mL of saturated sodium bicarbonate solution and extracted with dichloromethane (50 ml×3). The combined organic phase was washed with water (30 mL) and saturated sodium chloride solution (30 mL) successively, then dried over anhydrous magnesium 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 benzyl 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-(dimethylaminomethyl)-2,3-dihydrobenzofuran-4-carboxylate 29h (0.13 g, yield: 34.2%) as a white solid.

Workup

  1. temperatureThe reaction solution was heated
  2. temperatureto reflux for 3 hours
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting residue was added with 30 mL of saturated sodium bicarbonate solution
  5. extractionextracted with dichloromethane (50 ml×3)
  6. washThe combined organic phase was washed with water (30 mL) and saturated sodium chloride solution (30 mL) successively
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ef8def667a7d4192879cf8ffffe06171
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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