Hydrochloric Acid → 7-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

HRID 2364758Notes

Reaction equation

HRID 2364758 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]C)=[O:32])=[C:26]2[C:30]=1[O:29][CH2:28][CH2:27]2.Cl>C(O)C.O>[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]([OH:33])=[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 3

HCID 313Hydrochloric AcidHCID 68107686Methyl 7-amino-2,3-dihydrobenzofuran-4-carboxylateHCID 86668257(7S)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one

Product 1

HCID 681076557-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acidYield 62%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

(7S)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one 41f (300 mg, 1.70 mmol) and methyl 7-amino-2,3-dihydrobenzofuran-4-carboxylate 1g (543 mg, 1.80 mmol) were dissolved in 34 mL of the mixture solvent of ethanol and water (V/V=1:2.4) followed by the addition of 0.4 mL of concentrated hydrochloric acid and heated to reflux for 16 hours. The reaction solution was cooled down to room temperature, put into the refrigerator for 1 hour and filtered. The filter cake was washed with water (50 mL) and dissolved in 20 mL of the mixture solvent of water and 1 M lithium hydroxide (V/V=1:1), extracted with ethyl acetate (50 mL×2), the aqueous phase was added dropwise with 1 M hydrochloric acid to adjust pH to 2 resulting in the formation of precipitate. The precipitate was filtered to obtain the title compound 7-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 41g (0.45 g, yield: 62.0%) as a white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 16 hours
  3. filtrationfiltered
  4. washThe filter cake was washed with water (50 mL)
  5. dissolutiondissolved in 20 mL of the mixture solvent of water and 1 M lithium hydroxide (V/V=1:1)
  6. extractionextracted with ethyl acetate (50 mL×2)
  7. additionthe aqueous phase was added dropwise with 1 M hydrochloric acid
  8. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-af11ed7077bb4f48a0f834ba95815168
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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