Dichloromethane → 4-(2-(3,5-Dimethoxyphenethyl)-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl)picolinonitrile

HRID 1052293Notes

Reaction equation

HRID 1052293 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.CC1(C)C(C)(C)OB([C:40]2[CH:45]=[CH:44][N:43]=[C:42]([C:46]#[N:47])[CH:41]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C(#N)C.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].O>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([CH:17]=[C:16]([O:18][CH3:19])[CH:15]=1)[CH2:11][CH2:10][C:8]1[N:9]=[C:4]2[CH:3]=[C:2]([C:40]3[CH:45]=[CH:44][N:43]=[C:42]([C:46]#[N:47])[CH:41]=3)[N:22]([S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 457862934-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrileHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 899636914-(2-(3,5-Dimethoxyphenethyl)-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl)picolinonitrileYield 87.9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (60.0 mg, 0.119 mmol) (from Example 1, Step 4), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrile (0.041 g, 0.18 mmol from Combi-Blocks), sodium carbonate (25 mg, 0.24 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (20. mg, 0.024 mmol) in acetonitrile (1 mL)/water (0.2 mL) was evacuated and the refilled with N2 and then stirred at 100° C. for 3 hours. The mixture was diluted with ethyl acetate, washed with saturated NaHCO3, water, brine, then dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in methylene chloride (0-60%) to afford the desired product (0.055 g, 85%). LCMS calculated for C28H24N5O4S (M+H)+: m/z=526.2. Found 526.2.

Workup

  1. customwas evacuated
  2. additionthe refilled with N2
  3. additionThe mixture was diluted with ethyl acetate
  4. washwashed with saturated NaHCO3, water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in methylene chloride (0-60%)

Sources & evidence

ORD record
ord-f4b32c73e82d4acd9a872c6528e98413
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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