Sodium Carbonate → 2,6-Difluoro-3-[5-(4-pyridinyl)-1,3-benzothiazol-2-yl]methoxybenzenecarboxamide

HRID 415625Notes

Reaction equation

HRID 415625 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][O:11][C:12]3[C:13]([F:22])=[C:14]([C:19]([NH2:21])=[O:20])[C:15]([F:18])=[CH:16][CH:17]=3)=[N:7][C:6]=2[CH:23]=1.[N:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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:22][C:13]1[C:12]([O:11][CH2:10][C:8]2[S:9][C:5]3[CH:4]=[CH:3][C:2]([C:27]4[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=4)=[CH:23][C:6]=3[N:7]=2)=[CH:17][CH:16]=[C:15]([F:18])[C:14]=1[C:19]([NH2:21])=[O:20]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 462370143-(5-Bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide

Product 1

HCID 594028732,6-Difluoro-3-[5-(4-pyridinyl)-1,3-benzothiazol-2-yl]methoxybenzenecarboxamideYield 28%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-[(5-bromo-1,3-benzothiazol-2-yl)methoxy]-2,6-difluorobenzenecarboxamide (168 mg, 0.42 mmol, 1 equiv.), 4-pyridine boronic acid (98 mg, 0.63 mmol, 1.5 equiv.) and 2M aqueous Na2CO3 solution (0.42 ml, 0.82 mmol, 2 equiv.) were suspended in dioxane (3.5 ml) and the mixture was degassed and flushed with N2. Tetrakis(triphenylphosphine)palladium(0) catalyst (37 mg, 0.031 mmol, 0.075 equiv.) was added and the reaction mixture was heated under reflux for 12 h. After cooling at r.t., the mixture was diluted with H2O and the precipitant solid was filtered and rinsed with H2O, IMS, IMS/Et2O and Et2O. Re-crystallised from CH3CN, to give the desired product as an off-white solid, 47 mg (28% yield), mp 255-258° C. HPLC-MS: m/z 398 [M+H]+, Rt=3.28 min.

Workup

  1. customthe mixture was degassed
  2. customflushed with N2
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 12 h
  5. filtrationthe precipitant solid was filtered
  6. washrinsed with H2O, IMS, IMS/Et2O and Et2O

Sources & evidence

ORD record
ord-719ee7e3fef64055b3319088462d693d
Source dataset
uspto-grants-2012_01
Patent number
US08088791B2

Reaction notes

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