Tetrahydrofuran → HCID 24780526, compound

HRID 1507619Notes

Reaction equation

HRID 1507619 reaction equation
[CH:1]1([N:4]2[C:12](=[O:13])[C:11]3[NH:10][C:9]([C:14]4[CH:15]=[N:16][C:17]([NH:20][CH2:21][CH2:22][O:23][CH3:24])=[CH:18][CH:19]=4)=[N:8][C:7]=3[N:6]([CH2:25][CH2:26][CH3:27])[C:5]2=[O:28])[CH2:3][CH2:2]1.O1CCCC1.C(N(CC)C(C)C)(C)C.[F:43][C:44]1[CH:52]=[CH:51][C:47]([C:48](Cl)=[O:49])=[CH:46][N:45]=1>O>[CH:1]1([N:4]2[C:12](=[O:13])[C:11]3[NH:10][C:9]([C:14]4[CH:19]=[CH:18][C:17]([N:20]([CH2:21][CH2:22][O:23][CH3:24])[C:48](=[O:49])[C:47]5[CH:51]=[CH:52][C:44]([F:43])=[N:45][CH:46]=5)=[N:16][CH:15]=4)=[N:8][C:7]=3[N:6]([CH2:25][CH2:26][CH3:27])[C:5]2=[O:28])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 146236022-Fluoropyridine-5-carbonyl chlorideHCID 59648323HCID 59648323, compound

Product 1

HCID 24780526HCID 24780526, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

1-Cyclopropyl-8-[6-(2-methoxy-ethylamino)-pyridin-3-yl]-3-propyl-3,7-dihydro-purine-2,6-dione (2 g, 5.20 mmol) is charged to a reaction flask, followed by anhydrous tetrahydrofuran (25 ml) and N,N-diisopropylethylamine (5 eq). 6-fluoronicotinoyl chloride (1.16 g, 7.28 mmol, 1.4 eq) is added and the mixture is heated to 60° C. It is held for 12 hr and sampled for reaction completion via HPLC: When the reaction is complete, it is cooled to room temperature and water is added then filtered. The filtrate is concentrated then the resulting product is triturated with methanol at 60° C. then cooled to room temperature and filtered. The crude product was again triturated with methanol, filtered and again washed with methanol. The product is then dried at 50° C. to provide 2.41 g (91%). 1H NMR (400 MHz, DMSO-d6) δ 13.95 (1H), 8.9 (1H), 8.32 (1H), 8.15 (1H), 7.89 (1H), 7.39 (1H), 7.15 (1H), 4.2 (2H), 3.95 (2H), 3.6 (2H), 3.18 (3H), 2.6 (1H), 1.7 (2H), 1.05 (2H), 0.9 (3H), 0.7 (2H); m/z (ES+) 508.53

Workup

  1. aliquotsampled for reaction completion via HPLC
  2. temperatureit is cooled to room temperature
  3. filtrationthen filtered
  4. concentrationThe filtrate is concentrated
  5. customthe resulting product is triturated with methanol at 60° C.
  6. temperaturethen cooled to room temperature
  7. filtrationfiltered
  8. customThe crude product was again triturated with methanol
  9. filtrationfiltered
  10. washagain washed with methanol
  11. customThe product is then dried at 50° C.
  12. customto provide 2.41 g (91%)

Sources & evidence

ORD record
ord-5c9bfbdb364043dfb4adfccda3df2b34
Source dataset
uspto-grants-2015_12
Patent number
US09221821B2

Reaction notes

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