Sodium Hydroxide → 3-(2-(2,4-Difluorophenoxy)pyrido[3,2-d]pyridazin-5-yl)-4-methylbenzamide

HRID 1620411Notes

Reaction equation

HRID 1620411 reaction equation
Cl[C:2]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[F:20])=[N:11][C:6]=2[CH:5]=[N:4][N:3]=1.[CH3:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH2:28])=[O:27])=[CH:24][C:23]=1B1OC(C)(C)C(C)(C)O1.O.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CCO>[F:20][C:14]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=1[O:12][C:10]1[CH:9]=[CH:8][C:7]2[C:2]([C:23]3[CH:24]=[C:25]([CH:29]=[CH:30][C:22]=3[CH3:21])[C:26]([NH2:28])=[O:27])=[N:3][N:4]=[CH:5][C:6]=2[N:11]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 2735133Sodium Carbonate MonohydrateHCID 595448534-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 866645635-Chloro-2-(2,4-difluorophenoxy)pyrido[3,2-d]pyridazine

Product 1

HCID 462055133-(2-(2,4-Difluorophenoxy)pyrido[3,2-d]pyridazin-5-yl)-4-methylbenzamide

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-chloro-2-(2,4-difluorophenoxy)pyrido[3,2-d]pyridazine (Example 3, step 5; 130 mg, 0.44 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (144 mg, 0.55 mmol), sodium carbonate hydrate (220 mg, 1.77 mmol), and PdCl2(PPh3)2 (16 mg, 22 μmol) in DME:EtOH:H2O=7:2:3 (2.5 mL) was heated at 130° C. for 30 min in a microwave. The reaction mixture was treated with 5 mL of 1 N NaOH and extracted with EtOAc (2×20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. Purification on the ISCO (12 g column, eluted with 40-100% EtOAc in hexanes) afforded the title compound as a tan amorphous solid. MS (ESI, pos.ion) m/z: M+1=393.0

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification
  6. washon the ISCO (12 g column, eluted with 40-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1d7cd98ef09c4a60bfea0bafe03b51fa
Source dataset
uspto-grants-2014_07
Patent number
US08772481B2

Reaction notes

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