Potassium Phosphate, Tribasic → 1-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

HRID 710936

Reaction equation

HRID 710936 reaction equation
Br[C:2]1[N:7]2[N:8]=[C:9]([C:11]3([C:14]([OH:16])=[O:15])[CH2:13][CH2:12]3)[N:10]=[C:6]2[C:5]([O:17][CH3:18])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][CH:35]=2)[C:32](=[O:36])[O:31][CH2:30]3)O1.B([O-])[O-].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:18][O:17][C:5]1[C:6]2[N:7]([N:8]=[C:9]([C:11]3([C:14]([OH:16])=[O:15])[CH2:13][CH2:12]3)[N:10]=2)[C:2]([C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][CH:35]=2)[C:32](=[O:36])[O:31][CH2:30]3)=[CH:3][CH:4]=1

Participants

10

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 867645081-(5-Bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxylic acidHCID 178514824HCID 178514824, compound

Product 1

HCID 686549441-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

1-(5-Bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxylic acid (1.00 g, 3.20 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-isobenzofuran-1-one (preparation of the boronate was described in WO2011/134468) (1.67 g, 6.40 mmol) were dissolved in degassed dioxane (16 mL). Pd2(dba)3 (29 mg, 32 μmol), PCy3 (18 mg, 64 μmol) and K3PO4 (2.38 g, 11.2 mmol) were mixed in degassed water (10 mL). The two solutions were mixed and subsequently heated in a micro wave oven to 110° C. for 10 minutes, cooled to room temperature and diluted with EtOAc (40 mL). The organic phase was extracted with water (25 mL) and an aqueous 0.1 M solution of NaOH (25 mL) and the combined aqueous phases were acidified with conc. HCl to pH 0-1, and extracted with DCM (30 mL×4). Upon evaporation of the combined organic phases the title compound crystallized out (746 mg, 64%). HPLC-Retention time (XE Metode 7 CM): 1.97 minutes. Detected “M+1”-mass: 366.11. Calculated “M+1”-mass: 366.11. 1H NMR (DMSO, 300 MHz): δ=8.25-8.20 (m, 1H), 8.13 (dd, 1H, J=8.2, 1.4 Hz), 8.00 (d, 1H, J=8.0 Hz), 7.40 (d, 1H, J=8.2 Hz), 7.24 (d, 1H, J=8.3 Hz), 5.51 (s, 2H), 4.04 (s, 3H), 1.58-1.48 (m, 2H), 1.48-1.39 (m, 2H) ppm.

Workup

  1. additionThe two solutions were mixed
  2. temperaturecooled to room temperature
  3. extractionThe organic phase was extracted with water (25 mL)
  4. extractionextracted with DCM (30 mL×4)
  5. customUpon evaporation of the combined organic phases the title compound
  6. customcrystallized out (746 mg, 64%)
  7. custom1.97 minutes

Sources & evidence

ORD record
ord-afa63f2269334d41a114e04bb9857661
Source dataset
uspto-grants-2015_11
Patent number
US09181248B2

Linked notes

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