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

HRID 510145Notes

Reaction equation

HRID 510145 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[O:9])=[CH:6][N:5]=[C:4]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])[N:17]=2)[N:3]=1.[H-].[Na+].[C:35](N1C=CN=C1)(N1C=CN=C1)=[O:36]>C1COCC1>[F:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[CH2:25][N:18]1[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:24]2[C:16]([C:4]2[N:3]=[C:2]3[NH:1][C:35](=[O:36])[N:10]([CH2:11][C:12]([F:13])([F:14])[F:15])[C:8](=[O:9])[C:7]3=[CH:6][N:5]=2)=[N:17]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 666142844-Amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)pyrimidine-5-carboxamide

Product 1

HCID 666349057-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-3-(2,2,2-trifluoroethyl)pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

50 mg (0.11 mmol) of 4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)pyrimidine-5-carboxamide (example 103A) were initially charged in 5 ml of THF and, while cooling with ice, 18.0 mg (0.45 mmol) of sodium hydride (60% in mineral oil) were added over a period of 5 min. The mixture was stirred for 25 min, then 27.3 mg (0.17 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 and then the organic phase was diluted with 10 ml of THF. After drying with sodium sulfate, the volatile components were removed by means of a rotary evaporator. Then the crude material was purified by means of preparative HPLC [column: Reprosil C18, 10 μm, 250*30 mm; flow rate: 40 ml/min; eluent: methanol/0.05% formic acid; gradient: 50% methanol→95% methanol)]. The volatile components of the product fractions were removed on the rotary evaporator. Thus, 26 mg (48% 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. dry with materialAfter drying with sodium sulfate
  6. customthe volatile components were removed by means of a rotary evaporator
  7. customThen the crude material was purified by means of preparative HPLC [column
  8. customThe volatile components of the product fractions were removed on the rotary evaporator
  9. customThus, 26 mg (48% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-0432f6b453ae43c7ba1c482993ce1091
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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