Sodium Carbonate → HCID 44541043, compound

HRID 1695783Notes

Reaction equation

HRID 1695783 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][S:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])(=[O:13])=[O:12])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[CH3:22][C:23]1[S:24][CH:25]=[C:26]([C:28]([NH:30][C:31]2[C:32]3[C:36]([CH:37]=[C:38](B4OC(C)(C)CC(C)(C)O4)[CH:39]=2)=[N:35][N:34](C2CCCCO2)[CH:33]=3)=[O:29])[N:27]=1.C(=O)([O-])[O-].[Na+].[Na+].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].O>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[S:11]([NH:10][C:4]1[CH:3]=[C:2]([C:38]2[CH:37]=[C:36]3[C:32]([CH:33]=[N:34][NH:35]3)=[C:31]([NH:30][C:28]([C:26]3[N:27]=[C:23]([CH3:22])[S:24][CH:25]=3)=[O:29])[CH:39]=2)[CH:7]=[N:6][C:5]=1[O:8][CH3:9])(=[O:13])=[O:12]

Participants

7

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 59859951N-(5-bromo-2-methoxypyridin-3-yl)-2,4-difluorobenzenesulfonamide

Product 1

HCID 44541043HCID 44541043, compoundYield 15.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

N-[5-Bromo-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide (39 mg, 0.104 mmol), 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, 0.104 mmol), Pd(dppf)Cl2 (8 mg, 10.36 μmol) and sodium carbonate (44 mg, 0.415 mmol) were added to a microwave vial, followed by 1,4-Dioxane (0.5 mL) and Water (0.5 mL) and the reaction mixture was heated in the microwave at 140° C. for 20 min. After cooling, the mixture was then passed through a 1 g silica cartridge and washed with DCM:methanol. The solvent was evaporated by blow down under nitrogen. The residue was dissolved in 1.6 ml DMSO:methanol (1:1, v/v) and passed through a 1 g C18 cartridge, washing with acetonitrile, then evaporated by blow down. The residue was dissolved in 1.6 ml DMSO:methanol (1:1, v/v) and purified by MDAP (Method E). This MDAP purification step was then repeated to afford the title compound (9 mg).

Workup

  1. temperatureAfter cooling
  2. washwashed with DCM
  3. customThe solvent was evaporated by blow down under nitrogen
  4. dissolutionThe residue was dissolved in 1.6 ml DMSO:methanol (1:1
  5. washwashing with acetonitrile
  6. customevaporated by blow down
  7. dissolutionThe residue was dissolved in 1.6 ml DMSO:methanol (1:1
  8. customv/v) and purified by MDAP (Method E)
  9. customThis MDAP purification step

Sources & evidence

ORD record
ord-f147a6111ef14501a9b1f2ebd4923315
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

Loading…