Sodium Carbonate → HCID 58548065, compound

HRID 2207840Notes

Reaction equation

HRID 2207840 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][CH:9]2[CH2:12][N:11]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[CH2:10]2)=[CH:4][C:3]=1I.ClC1N=NC(OC2CN([C:36]3[CH:45]=[CH:44][C:43]4[C:38](=CC=CC=4)[N:37]=3)C2)=C(I)C=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:53][C:54]1(C)C(C)(C)OB(C2CCN(C(OC(C)(C)C)=O)CC=2)[O:55]1>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[N:11]1[CH2:12][CH:9]([O:8][C:5]2[N:6]=[N:7][CH:2]=[CH:3][C:4]=2[CH:44]2[CH2:45][CH2:36][N:37]([C:54](=[O:55])[CH3:53])[CH2:38][CH2:43]2)[CH2:10]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 58547917HCID 58547917, compoundHCID 58547958HCID 58547958, compound

Product 1

HCID 58548065HCID 58548065, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-(3-((6-chloro-5-iodopyridazin-3-yl)oxy)azetidin-1-yl)quinoline and 2-(3-((6-chloro-4-iodopyridazin-3-yl)oxy)azetidin-1-yl)quinoline as isomeric mixture, (see PREPARATION P6.1; 521 mg, 1.2 mmol) in 1,4-dioxane (15 mL) was treated with Na2CO3 (255 mg, 2.4 mmol) in 2 mL of water as a solution, followed by additional of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (557 mg, 1.8 mmol) and Pd(dppf)Cl2 (88 mg, 0.12 mmol). The resulting mixture was heated at refluxing overnight under N2 atmosphere. The solution was filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography on silica gel (20% to 70% EtOAc in petroleum ether) to give the title product (509 mg, 1.0 mmol, yield: 83%). ESI-MS (M+1): 494 calc. for C26H28ClN5O3 493.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat refluxing overnight under N2 atmosphere
  3. filtrationThe solution was filtered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by flash column chromatography on silica gel (20% to 70% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-50e03f6163094efeb3be04b7fc72b7f1
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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