HCID 86670204, compound → HCID 57410026, compound

HRID 2046225Notes

Reaction equation

HRID 2046225 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][CH2:9][C:10]2[CH:26]=[C:13]3[C:14](=[O:25])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[CH2:16][CH2:17][N:12]3[N:11]=2)=[CH:4][CH:3]=1>CO.C1COCC1.O.[Pd]>[NH4+:6].[OH-:8].[F:24][C:21]1[CH:20]=[CH:19][C:18]([N:15]2[CH2:16][CH2:17][N:12]3[N:11]=[C:10]([CH2:9][O:8][C:5]4[N:6]=[N:7][CH:2]=[CH:3][CH:4]=4)[CH:26]=[C:13]3[C:14]2=[O:25])=[CH:23][CH:22]=1

Participants

7

Reactant 1

HCID 86670204HCID 86670204, compound

Product 2

HCID 14923Ammonium HydroxideHCID 57410026HCID 57410026, compoundYield 50.1%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

2-(6-Chloro-pyridazin-3-yloxymethyl)-5-(4-fluoro-phenyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (74 mg, 0.2 mmol) was dissolved in a mixture of TEA (0.2 mL), MeOH (1.6 mL) and THF (2.4 mL). The solution was hydrogenated in a H-Cube reactor (1 ml/min, 30 mm 10% Pd/C cartridge, full H2 mode, 40° C., 1 cycle). The solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 N solution of ammonia in MeOH in DCM 0/100 to 10/90). The desired fractions were collected and the solvents evaporated in vacuo. The product was repurified by RP HPLC on (C18 XBridge 30×100 5 um). Mobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 20% MeOH to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 100% MeOH) to yield 5-(4-fluoro-phenyl)-2-(pyridazin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (17 mg, 24% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.18 (dd, J=6.8, 5.2 Hz, 2H), 4.56 (dd, J=6.8, 5.2 Hz, 2H), 5.64 (s, 2H), 7.05 (dd, J=9.0, 1.4 Hz, 1H), 7.08 (s, 1H), 7.09-7.17 (m, 2H), 7.29-7.35 (m, 2H), 7.40 (dd, J=8.9, 4.5 Hz, 1H), 8.88 (dd, J=4.4, 1.4 Hz, 1H).

Workup

  1. customThe solution was hydrogenated in a H-Cube reactor
  2. customThe solvents were evaporated in vacuo
  3. customThe crude product was purified by flash column chromatography (silica; 7 N solution of ammonia in MeOH in DCM 0/100 to 10/90)
  4. customThe desired fractions were collected
  5. customthe solvents evaporated in vacuo
  6. customThe product was repurified by RP HPLC on (C18 XBridge 30×100 5 um)

Sources & evidence

ORD record
ord-8732bfc19f014f48bb5487480069cee4
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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