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

HRID 244754

Reaction equation

HRID 244754 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]=[C:43]([C:45]#[N:46])[CH:42]=[C:41]2[C:37]=1[CH:38]=[CH:39][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]>[C:45]([C:43]1[CH:42]=[C:41]2[C:37]([CH:38]=[CH:39][NH:40]2)=[C:36]([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:44]=1)#[N:46]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 247288834-bromo-1H-indole-6-carbonitrileHCID 58255833HCID 58255833, compound

Product 1

HCID 58356433N-[6-(6-cyano-1H-indol-4-yl)-1H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamideYield 53.1%

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-1H-indole-6-carbonitrile (252 mg, 0.114 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 methanol. The solvent was 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 F). To the sample-containing fractions 2M HCl (aq) (ca. 1 ml) was added and the fractions were blown down. The residue was dissolved in DCM:methanol (ca. 50:50, v/v) and passed through a 1 g PS—NH2 cartridge, washing with DCM:methanol. Solvent was removed by blow down then the residue was suspended in 2 ml dioxane:water (1:1, v/v) and freeze dried to afford the title compound as a white solid (22 mg).

Workup

  1. temperaturecooled
  2. washwas washed with methanol
  3. customThe solvent was evaporated by blow down
  4. dissolutionThe residue was dissolved in 1.6 ml DMSO:methanol (1:1
  5. customv/v) and purified by Mass Directed Auto Preparative HPLC (Method F)
  6. additionTo the sample-containing fractions 2M HCl (aq) (ca. 1 ml) was added
  7. dissolutionThe residue was dissolved in DCM
  8. washwashing with DCM
  9. customSolvent was removed by blow down then the residue
  10. customv/v) and freeze dried

Sources & evidence

ORD record
ord-8e659aab6be146918a074e1a2d2a4fce
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Linked notes

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