1,2-Dimethoxyethane → HCID 58072375, compound

HRID 1895337Notes

Reaction equation

HRID 1895337 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:18]=[C:17]([O:19][CH3:20])[C:16](=[O:21])[C:15]([C:22]3[N:26]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[N:25]=[CH:24][CH:23]=3)=[N:14]2)=[C:9]([F:33])[CH:8]=1)(=O)=O.[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:33][C:9]1[CH:8]=[C:7]([C:40]2[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=2)[CH:12]=[CH:11][C:10]=1[N:13]1[CH:18]=[C:17]([O:19][CH3:20])[C:16](=[O:21])[C:15]([C:22]2[N:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:25]=[CH:24][CH:23]=2)=[N:14]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 580722213-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl trifluoromethanesulfonate

Product 1

HCID 58072375HCID 58072375, compoundYield 81.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Procedure

A mixture of 3-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl trifluoromethanesulfonate (230 mg, 0.45 mmol), 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (104 mg, 0.50 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol), Na2CO3 (106 mg, 1.0 mmol), DME (4 mL), and H2O (1 mL) was refluxed overnight under Ar atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with THF and recrystallized from MeOH/H2O to give the title compound (162 mg, 81% yield) as a white solid: mp 195-197° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.91 (3H, s), 3.96 (3H, s), 6.38 (1H, t, J=8.3 Hz), 7.06 (1H, ddd, J=0.8, 1.9, 8.3 Hz), 7.23 (1H, dd, J=1.9, 12.8 Hz), 7.30 (1H, d, J=1.9 Hz), 7.36-7.47 (5H, m), 7.64 (1H, s), 7.74 (1H, d, J=0.8 Hz), 7.79 (1H, d, J=1.9 Hz), 7.81 (1H, d, J=2.6 Hz). LC-MS (ESI) m/z 443 [M+H]+. Anal. Calcd for C24H19FN6O2: C, 65.15; H, 4.33; N, 18.99. Found: C, 65.15; H, 4.30; N, 19.02.

Workup

  1. temperaturewas refluxed overnight under Ar atmosphere
  2. extractionextracted with AcOEt
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography
  7. washeluting with THF
  8. customrecrystallized from MeOH/H2O

Sources & evidence

ORD record
ord-e96424b9c8e943268a03b2db54bb84d2
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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