Dichloromethane → 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

HRID 1052268Notes

Reaction equation

HRID 1052268 reaction equation
Br[C:2]1[N:22]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:5]2=[N:6][CH:7]=[C:8]([CH2:10][CH2:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=3)[N:9]=[C:4]2[CH:3]=1.[CH3:32][N:33]1[CH2:38][CH2:37][N:36]([C:39]2[CH:44]=[CH:43][C:42](B3OC(C)(C)C(C)(C)O3)=[CH:41][CH:40]=2)[CH2:35][CH2:34]1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].O1CCOCC1>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:4]3[CH:3]=[C:2]([C:42]4[CH:41]=[CH:40][C:39]([N:36]5[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]5)=[CH:44][CH:43]=4)[N:22]([S:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)(=[O:25])=[O:24])[C:5]3=[N:6][CH:7]=2)[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 179989051-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazineHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 899631342-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazineYield 636.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
88 °C

Procedure

A stirred mixture of 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (from Example 1, step 4, 30.0 mg, 59.7 μmol), 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine (from Alfa Aesar, cat# H51659, 19.8 mg, 6.57 μmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (4.9 mg, 5.97 mmol), and potassium phosphate (25.4 mg, 119 μmol) in water (0.2 mL)/1,4-dioxane (1 mL) was heated at 88° C. After another 1 hour, the reaction mixture was quenched with saturated aq. NH4Cl, extracted with methylene chloride. The combined organic layers were dried over MgSO4, then concentrated to give the desired product (25 mg, 70%). LCMS calculated for C33H36N5O4S (M+H)+: m/z=598.3. Found: 598.3.

Workup

  1. customthe reaction mixture was quenched with saturated aq. NH4Cl
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-9e2d95fc17f04cd19d27495d9c87b0c4
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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