Sodium Hydroxide → N-[5-[4-(5-{[(3R,5S)-3,5-Dimethyl-4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide

HRID 38886

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2S(C2C=CC=CC=2)(=O)=O)=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][C@H:30]([CH3:32])[N:29]([CH:33]([CH3:35])[CH3:34])[C@H:28]([CH3:36])[CH2:27]3)=[N:23][N:24]=2)[CH:3]=1.[F:37][C:38]1[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=1[S:45]([NH:48][C:49]1[C:50]([O:64][CH3:65])=[N:51][CH:52]=[C:53](B2OC(C)(C)C(C)(C)O2)[CH:54]=1)(=[O:47])=[O:46].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>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]>[CH3:36][C@H:28]1[N:29]([CH:33]([CH3:35])[CH3:34])[C@@H:30]([CH3:32])[CH2:31][N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:53]4[CH:54]=[C:49]([NH:48][S:45]([C:39]5[CH:40]=[CH:41][C:42]([F:44])=[CH:43][C:38]=5[F:37])(=[O:47])=[O:46])[C:50]([O:64][CH3:65])=[N:51][CH:52]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][NH:8]4)=[N:24][N:23]=2)[CH2:27]1

Participants

Conditions

Temperature: 100 °C

Procedure

6-Bromo-4-(5-{[(3R,5S)-3,5-dimethyl-4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (172 mg, 0.300 mmol), 2,4-difluoro-N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]benzenesulfonamide (128 mg, 0.300 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (43.9 mg, 0.060 mmol) and potassium phosphate tribasic (191 mg, 0.900 mmol) were added to a microwave vial and dissolved in 1,4-dioxane (2.5 ml) and water (0.25 ml). The mixture was heated under microwave irradiation at 100° C. for 20 mins. The mixture was passed through a 1 g silica SPE cartridge, washing with MeOH. The solvent was removed under a stream of nitrogen and the residue was partitioned between DCM (10 ml) and water (10 ml), separated with a hydrophobic frit and the solvent again removed under a stream of nitrogen. The protected compound was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml, 2.000 mmol) and stirred at room temperature for 4 h. The mixture was evaporated to dryness under a stream of nitrogen. The residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml) and separated with a hydrophilic frit. The solvent was removed under a stream of nitrogen and the residue was dissolved in DMSO (1 ml) and purified by purified by Mass Directed Automated Preparative HPLC. The appropriate fraction was blown down under a stream of nitrogen to give the title compound as a pale yellow solid (4.9 mg).

Workup

washwashing with MeOH
customThe solvent was removed under a stream of nitrogen
customthe residue was partitioned between DCM (10 ml) and water (10 ml)
customseparated with a hydrophobic frit
customthe solvent again removed under a stream of nitrogen
dissolutionThe protected compound was dissolved in 1,4-dioxane (1 ml)
customThe mixture was evaporated to dryness under a stream of nitrogen
customThe residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml)
customseparated with a hydrophilic frit
customThe solvent was removed under a stream of nitrogen
dissolutionthe residue was dissolved in DMSO (1 ml)
custompurified
customby purified by Mass Directed Automated Preparative HPLC

Sources & evidence

ORD record: ord-54f25f19f5a14d4face657ced93290d2
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524751B2

Linked notes

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