Cesium carbonate → 2-(benzyloxy)-5-(2-methoxypyrimidin-4-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1396507Notes

Reaction equation

HRID 1396507 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:12]2[C:13](=[O:17])[NH:14][CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([O:26][CH3:27])[N:21]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]1[CH:18]=[C:12]2[C:13](=[O:17])[N:14]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([O:26][CH3:27])[N:21]=3)[CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5752304-Chloro-2-methoxypyrimidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 727147872-(benzyloxy)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

Product 1

HCID 727147842-(benzyloxy)-5-(2-methoxypyrimidin-4-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-oneYield 35.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Palladium (II) acetate (2.8 mg, 0.012 mmol) was added to a stirred suspension of 2-(benzyloxy)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.1 g, 0.41 mmol), 4-chloro-2-methoxy-pyrimidine (0.120 g, 0.82 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (17.7 mg, 0.037 mmol) and Cs2CO3 (0.19 g, 0.58 mmol) in 1,4-dioxane (2 mL). The mixture was stirred at 100° C. for 24 hours. The solvent was evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 95/5). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with diethyl ether to yield 2-(benzyloxy)-5-(2-methoxypyrimidin-4-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (51 mg, 35% yield) as a white solid. C18H12N5O3. 1H NMR (500 MHz, CDCl3) δ ppm 4.03 (s, 3H), 4.33 (dd, J=6.6, 5.2 Hz, 2H), 4.64 (dd, J=6.6, 5.2 Hz, 2H), 5.23 (s, 2H), 6.40 (s, 1H), 7.31-7.36 (m, 1H), 7.39 (t, J=7.4 Hz, 2H), 7.42-7.48 (m, 2H), 7.89 (d, J=5.8 Hz, 1H), 8.44 (d, J=5.8 Hz, 1H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customThe crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 95/5)
  3. customThe desired fractions were collected
  4. customthe solvents evaporated in vacuo
  5. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-acf80fc91d174bd182516d1ca31aa2f3
Source dataset
uspto-grants-2014_12
Patent number
US08901125B2

Reaction notes

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