Water → 7-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione

HRID 510146Notes

Reaction equation

HRID 510146 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([NH2:10])=[O:9])=[CH:6][N:5]=[C:4]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[N:12]=2)[N:3]=1.[H-].[Na+].[C:30](N1C=CN=C1)(N1C=CN=C1)=[O:31].O>C1COCC1>[F:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH2:20][N:13]1[C:14]2=[N:15][CH:16]=[CH:17][CH:18]=[C:19]2[C:11]([C:4]2[N:3]=[C:2]3[NH:1][C:30](=[O:31])[NH:10][C:8](=[O:9])[C:7]3=[CH:6][N:5]=2)=[N:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 98853504-Amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-5-carboxamide

Product 1

HCID 666143167-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

70 mg (0.19 mmol) of 4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-5-carb oxamide (example 104A) were initially charged in 7 ml of THF and, while cooling with ice, 30.8 mg (0.77 mmol) of sodium hydride (60% in mineral oil) were added over a period of 5 min. The mixture was stirred for 25 min, then 46.9 mg (0.29 mmol) of 1,1′-carbonyldiimidazole were added with ice cooling over 5 min. Conversion was effected at room temperature for 1 h and at reflux temperature for 90 min. After cooling, the mixture was hydrolyzed with 2 ml of water. The precipitate formed was filtered off and then stirred in 7 ml of methanol/water (5/2). The remaining precipitate was filtered off and dried under high vacuum. Thus, 26 mg (35% of theory) of the target compound were obtained.

Workup

  1. additionwere added over a period of 5 min
  2. waitConversion was effected at room temperature for 1 h
  3. temperatureat reflux temperature for 90 min
  4. temperatureAfter cooling
  5. customThe precipitate formed
  6. filtrationwas filtered off
  7. stirringstirred in 7 ml of methanol/water (5/2)
  8. filtrationThe remaining precipitate was filtered off
  9. customdried under high vacuum
  10. customThus, 26 mg (35% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-7e1fcfb065da469ebc469ccf366b132c
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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