Potassium Carbonate → 3-{[6-(azetidin-1-ylcarbonyl)pyridazin-3-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1989999Notes

Reaction equation

HRID 1989999 reaction equation
[N:1]1([C:5]([C:7]2[N:8]=[N:9][C:10](Cl)=[CH:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[OH:14][C:15]1[CH:16]=[C:17]([CH:27]=[C:28]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:29]=1)[C:18]([NH:20][C:21]1[CH:25]=[CH:24][N:23]([CH3:26])[N:22]=1)=[O:19].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[N:1]1([C:5]([C:7]2[N:8]=[N:9][C:10]([O:14][C:15]3[CH:16]=[C:17]([CH:27]=[C:28]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:29]=3)[C:18]([NH:20][C:21]3[CH:25]=[CH:24][N:23]([CH3:26])[N:22]=3)=[O:19])=[CH:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 536296743-(Azetidin-1-ylcarbonyl)-6-chloropyridazineHCID 591271783-hydroxy-5-{[(2S)-1-methoxypropan-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 160399693-{[6-(azetidin-1-ylcarbonyl)pyridazin-3-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 90.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3-(azetidin-1-ylcarbonyl)-6-chloropyridazine (45 mg, 0.23 mmol), 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (70 mg, 0.23 mmol) and potassium carbonate (63 mg, 0.46 mmol) in acetonitrile (3 mL) was stirred in a Smith Creator microwave at 130° C. for 1 hour. The solid was filtered off and the solvent was removed in vacuo. The residue was purified by reverse phase preparative HPLC, eluting with 5-95% acetonitrile in water (+0.2% TFA), followed by passage through a Silicycle Si-Carbonate cartridge, eluting with methanol, to give the desired product as a colourless solid (97 mg). 1H NMR δ (CDCl3): 1.34 (3H, d), 1.66 (3H, s), 2.33-2.41 (2H, m), 3.40 (3H, s), 3.48-3.52 (1H, m), 3.56-3.60 (1H, m), 3.79 (3H, s), 4.27 (2H, d), 4.58-4.62 (1H, m), 4.76 (2H, t), 6.79 (1H, d), 6.97 (1H, t), 7.25-7.29 (3H, m), 7.35-7.36 (1H, m), 8.26-8.28 (1H, m), 8.49 (1H, s); m/z 467 (M+H)+.

Workup

  1. filtrationThe solid was filtered off
  2. customthe solvent was removed in vacuo
  3. customThe residue was purified by reverse phase preparative HPLC
  4. washeluting with 5-95% acetonitrile in water (+0.2% TFA)
  5. washeluting with methanol

Sources & evidence

ORD record
ord-e4d781f9e24945e58424e4a61f3734be
Source dataset
uspto-grants-2010_01
Patent number
US07642263B2

Reaction notes

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