Potassium Phosphate, Tribasic → 6-(1H-Indol-4-yl)-1-[(4-methylphenyl)sulfonyl]-4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole

HRID 38813Notes

Reaction equation

HRID 38813 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:21]2[O:22][C:23]([CH2:26][N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[N:24][N:25]=2)[CH:3]=1.CC1(C)C(C)(C)OB([C:41]2[CH:49]=[CH:48][CH:47]=[C:46]3[C:42]=2[CH:43]=[CH:44][NH:45]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH:45]1[C:46]2[C:42](=[C:41]([C:2]3[CH:10]=[C:9]4[C:5]([CH:6]=[N:7][N:8]4[S:11]([C:14]4[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=4)(=[O:13])=[O:12])=[C:4]([C:21]4[O:22][C:23]([CH2:26][N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)=[N:24][N:25]=4)[CH:3]=3)[CH:49]=[CH:48][CH:47]=2)[CH:43]=[CH:44]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 666958226-Bromo-1-[(4-methylphenyl)sulfonyl]-4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole

Product 1

HCID 667766026-(1H-Indol-4-yl)-1-[(4-methylphenyl)sulfonyl]-4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazoleYield 29.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of 6-bromo-1-[(4-methylphenyl)sulfonyl]-4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole (75 mg, 0.145 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (52.8 mg, 0.217 mmol), 1,1′-bis(diphenylphosphino)-ferrocene palladium dichloride (5.29 mg, 7.23 μmol) and tripotassium phosphate (92 mg, 0.434 mmol) in 1,4-dioxane (2 ml) and water (0.2 ml) was heated at 100° C. in the microwave (Biotage initiator) for 30 mins. The mixture was poured into water (40 ml) and extracted into ethyl acetate (2×30 ml). The combined extracts were washed with water (30 ml), dried (frit) and evaporated. The residual solid was purified on a silica (5 g) cartridge using ether and ethyl acetate/ether (2:1) as the eluent. The appropriate fractions were evaporated to dryness to give the title compound as a cream coloured solid (24 mg).

Workup

  1. extractionextracted into ethyl acetate (2×30 ml)
  2. washThe combined extracts were washed with water (30 ml)
  3. customdried (frit)
  4. customevaporated
  5. customThe residual solid was purified on a silica (5 g) cartridge
  6. customThe appropriate fractions were evaporated to dryness

Sources & evidence

ORD record
ord-8c36e0612faa450d8a35ad3ce46c7a8c
Source dataset
uspto-grants-2013_09
Patent number
US08524751B2

Reaction notes

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