Dichloromethane → 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine

HRID 1052252Notes

Reaction equation

HRID 1052252 reaction equation
Br[C:2]1[N:22](S(C2C=CC=CC=2)(=O)=O)[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.ClCCl.[O:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:43]=[N:42]2)[CH2:37][CH2:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>O.Cl[Pd]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].O1CCOCC1>[CH3:19][O:18][C:16]1[CH:17]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:4]3[CH:3]=[C:2]([C:44]4[CH:43]=[N:42][N:41]([CH:38]5[CH2:39][CH2:40][O:35][CH2:36][CH2:37]5)[CH:45]=4)[NH:22][C:5]3=[N:6][CH:7]=2)[CH:13]=[C:14]([O:20][CH3:21])[CH:15]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 457884961-(Tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 730562402-[2-(3,5-dimethoxyphenyl)ethyl]-6-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-5H-pyrrolo[2,3-b]pyrazineYield 19.4%

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 (15.0 mg, 29.8 μmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complexed with dichloromethane (1:1) (1.30 mg, 1.59 μmol), 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.9 mg, 32.0 μmol), and potassium phosphate (13.5 mg, 63.6 μmol) in water (0.2 mL)/1,4-dioxane (0.40 mL) was heated at 88° C. After 1 hour, the volatiles were removed under vacuum and the residues were dissolved in methanol (1 mL). Potassium carbonate (8.8 mg, 63.7 μmol) was added and the reaction mixture was then warmed up to 60° C. After 1 hour, the reaction mixture was cooled to ambient temperature and was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (2.5 mg) as its TFA salt. LCMS calculated for C24H28N5O3 (M+H)+: m/z=434.2. Found: 434.2.

Workup

  1. customthe volatiles were removed under vacuum
  2. dissolutionthe residues were dissolved in methanol (1 mL)
  3. temperaturethe reaction mixture was then warmed up to 60° C
  4. waitAfter 1 hour
  5. temperaturethe reaction mixture was cooled to ambient temperature
  6. customwas purified on RP-HPLC (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-9119fed60c0e4933a3edb4fe29b1b3b6
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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