2-(Propane-2-sulfonyl)aniline → Methyl 4'-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

HRID 1664689

Reaction equation

HRID 1664689 reaction equation
Br[C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]([NH:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][C:13]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=3)=[C:12]([CH3:28])[CH:11]=2)[CH:3]=1.[CH:29]([S:32]([C:35]1[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=1[NH2:37])(=[O:34])=[O:33])([CH3:31])[CH3:30].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[Cl:8][C:7]1[C:2]([NH:37][C:36]2[CH:38]=[CH:39][CH:40]=[CH:41][C:35]=2[S:32]([CH:29]([CH3:31])[CH3:30])(=[O:34])=[O:33])=[CH:3][C:4]([NH:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][C:13]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=3)=[C:12]([CH3:28])[CH:11]=2)=[N:5][CH:6]=1

Participants

7

Reactant 4

HCID 126463662-(Propane-2-sulfonyl)anilineHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 23676156Sodium t-butoxideHCID 59764478Methyl 4'-(4-bromo-5-chloropyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

Product 1

HCID 59764572Methyl 4'-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

Methyl 4′-(4-bromo-5-chloropyridin-2-ylamino)-5′-methoxy-2′-methylbiphenyl-4-carboxylate generated in Step 2 (9 mg, 0.022 mmol), 2-(isopropylsulfonyl)aniline (4 mg, 0.022 mmol, 1 equiv), Pd2(dba)3 (1.7 mg, 0.002 mmol, 0.1 equiv.), 2-(Dicyclohexylphosphino)-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (1.8 mg, 0.004 mmol, 0.2 equiv.), and Sodium tert-butoxide (2.7 mg, 0.028 mmol, 1.3 equiv.) are added to THF (1 mL). The resulting mixture is bubbled with N2 gas for 5 minutes and then heated at 150° C. for 4 hours. After cooling to room temperature, the reaction mixture is diluted into EtOAc and washed with H2O. The EtOAc layer is dried over Mg2SO4 and concentrated in vacuo. Silica gel chromatography (hexanes-EtOAc) affords Methyl 4′-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyridin-2-ylamino)-5′-methoxy-2′-methylbiphenyl-4-carboxylate (254); MS m/z 580.2 (M+1).

Workup

  1. customThe resulting mixture is bubbled with N2 gas for 5 minutes
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture is diluted into EtOAc
  4. washwashed with H2O
  5. dry with materialThe EtOAc layer is dried over Mg2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-830d7e361cb342fca5f70b840c7fcd68
Source dataset
uspto-grants-2011_10
Patent number
US08039479B2

Linked notes

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