Sodium Carbonate → HCID 44539933, compound

HRID 1695792Notes

Reaction equation

HRID 1695792 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[C:11]3[C:15]([CH:16]=[C:17](B4OC(C)(C)CC(C)(C)O4)[CH:18]=2)=[N:14][N:13](C2CCCCO2)[CH:12]=3)=[O:8])[N:6]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:42]1[CH:43]=[C:44]([NH:49][S:50]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[CH3:59])(=[O:52])=[O:51])[C:45]([Cl:48])=[N:46][CH:47]=1.O1CCOCC1>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].C(Cl)Cl.CO.O>[Cl:48][C:45]1[N:46]=[CH:47][C:42]([C:17]2[CH:16]=[C:15]3[C:11]([CH:12]=[N:13][NH:14]3)=[C:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[O:8])[CH:18]=2)=[CH:43][C:44]=1[NH:49][S:50]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[CH3:59])(=[O:52])=[O:51]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 582558332-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamideHCID 86653305HCID 86653305, compound

Product 1

HCID 44539933HCID 44539933, compoundYield 32.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
140 °C

Procedure

2-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg), Pd(dppf)Cl2 (7.6 mg) and sodium carbonate (44 mg) were added to a 0.5-2 ml microwave vial. N-(5-Bromo-2-chloro-3-pyridinyl)-2-methylbenzenesulfonamide (37.5 mg) was added followed by 1,4-dioxane (0.5 ml) and water (0.5 ml). The reaction was heated at 140° C. for 20 min. The material was passed though a 1 g silica cartridge with DCM/methanol, then evaporated to dryness. The residue was dissolved in 1.6 ml DMSO:methanol (1:1, v/v), passed through a 1 g C18 cartridge, washing with acetonitrile and then evaporated in the blow down. The residue was dissolved in 1.6 ml DMSO:methanol (1:1, v/v) and purified by MDAP (method F). Pure fractions were combined, blown down, suspended in ca. 3 ml dioxane:water (1:1, v/v) and freeze-dried to give title compound (18 mg)

Workup

  1. customevaporated to dryness
  2. dissolutionThe residue was dissolved in 1.6 ml DMSO:methanol (1:1
  3. washwashing with acetonitrile
  4. customevaporated in the blow down
  5. dissolutionThe residue was dissolved in 1.6 ml DMSO:methanol (1:1
  6. customv/v) and purified by MDAP (method F)
  7. customv/v) and freeze-dried

Sources & evidence

ORD record
ord-fdb344550b4a4104a5518c02ce200301
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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