Tributylborane → HCID 67012329, compound

HRID 2356586Notes

Reaction equation

HRID 2356586 reaction equation
[CH3:1][CH:2]([CH3:32])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[S:27](C)(=[O:29])=[O:28])[CH2:16][CH2:15]2)=[CH:12][CH:13]=1)=[O:7].C[Mg]Cl.C(B(CCCC)CCCC)CCC.C([O-])(=O)C.[Na+].[NH2:54]OS(O)(=O)=O>C1COCC1.C(OCC)(=O)C.O>[CH3:1][CH:2]([CH3:32])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[S:27](=[O:29])(=[O:28])[NH2:54])[CH2:16][CH2:15]2)=[CH:12][CH:13]=1)=[O:7]

Participants

9

Reactant 5

HCID 31216TributylboraneHCID 76284hydroxylamine-O-sulfonic acidHCID 517045Sodium AcetateHCID 668499076-[4-(2-METHANESULFONYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid (3-METHYLBUTYL)AMIDEHCID 178418332HCID 178418332, compound

Product 1

HCID 67012329HCID 67012329, compoundYield 42.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of 6-[4-(2-methanesulfonylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (3-methylbutyl)amide (0.078 g, 0.17 mmol) in 5 mL of THF cooled was added methyl magnesium chloride (0.071 mL, 0.212 mmol). The resulting mixture was stirred for 15 minutes at 0° C., and then 30 minutes at ambient temperature. The reaction mixture was cooled to 0° C. again, then tributylborane (0.255 mL, 0.255 mmol) was added. The mixture was stirred at ambient temperature for 30 minutes, then heated to reflux for 18 h. After the mixture was cooled to 0° C., sodium acetate, water and hydroxylamine-o-sulfonic acid (0.067 g) were added. The mixture was stirred for 3 h, and then diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine, dried and concentrated in vacuo. The residue was purified by flash column chromatography using 20% methanol in ethyl acetate to yield the title product (0.033 g, 42% yield). 1H NMR (300 MHz, CDCl3) δ 8.58, 7.98, 7.81, 7.75-7.68, 7.64-7.58, 7.43, 7.19, 4.03-3.88, 3.78-3.59, 3.21-3.20, 3.152-3.147, 1.65-1.50, 1.46-1.35, 0.85. 13C NMR (75 MHz, CDCl3) δ 170.1, 165.5, 161.7, 146.3, 139.1, 137.3, 135.5, 131.3, 130.9, 128.8, 127.9, 114.4, 45.6, 45.2, 44.96, 42.6, 39.5, 38.8, 27.1, 22.9. MS (ES+) m/z 460.1 (M+1).

Workup

  1. custom30 minutes
  2. customat ambient temperature
  3. temperatureThe reaction mixture was cooled to 0° C. again
  4. stirringThe mixture was stirred at ambient temperature for 30 minutes
  5. temperatureheated
  6. temperatureto reflux for 18 h
  7. temperatureAfter the mixture was cooled to 0° C.
  8. stirringThe mixture was stirred for 3 h
  9. washwashed with saturated sodium bicarbonate, brine
  10. customdried
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-c587d84721cf48afaa35ff7ccbb07352
Source dataset
uspto-grants-2010_07
Patent number
US07759348B2

Reaction notes

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