Sodium Carbonate → 2-methyl-N-[6-(2-methyl-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 244753Notes

Reaction equation

HRID 244753 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.Br[C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[CH:38]=[C:39]([CH3:45])[NH:40]2.C(=O)([O-])[O-].[Na+].[Na+]>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]>[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([C:36]3[CH:44]=[CH:43][CH:42]=[C:41]4[C:37]=3[CH:38]=[C:39]([CH3:45])[NH:40]4)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][NH:14]3)=[O:8])[N:6]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 218145664-Bromo-2-methyl-1H-indoleHCID 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-carboxamide

Product 1

HCID 583564532-methyl-N-[6-(2-methyl-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamideYield 42.2%

Reagents, catalysts & solvents 3

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

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, 0.104 mmol), 4-bromo-2-methyl-1H-indole (22 mg, 0.104 mmol), Pd(dppf)Cl2 (8 mg, 0.01 mmol) and sodium carbonate (44 mg, 0.415 mmol) were added to a 0.5-2 ml microwave vial and suspended in 1,4-dioxane (0.5 mL) and water (0.5 mL). The mixture was heated in the microwave at 140° C. for 20 min, then cooled and passed through a 1 g silica cartridge which was washed with DCM:methanol. The solvent was evaporated by blow down. 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 evaporated by blow down. The residue was dissolved in 1.6 ml DMSO:methanol (1:1, v/v) and purified by Mass Directed Auto Preparative HPLC (Method G). Pure fractions were combined, evaporated to dryness, the residue suspended in 3 ml dioxane:water (1:1, v/v) and freeze dried to afford the title compound as an off-white solid (17 mg).

Workup

  1. temperaturecooled
  2. washwas washed with DCM
  3. customThe solvent was evaporated by blow down
  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 Mass Directed Auto Preparative HPLC (Method G)
  9. customevaporated to dryness
  10. customv/v) and freeze dried

Sources & evidence

ORD record
ord-bf5b945b57504143ae057d0222e7eeed
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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