Potassium Carbonate → 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-{[(1-methylethyl)amino]methyl}-3-pyridinyl)-1H-indole-7-carboxamide

HRID 562179Notes

Reaction equation

HRID 562179 reaction equation
[CH3:1][CH:2]([NH:4][CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:11]=1)[CH3:3].Br[C:22]1[CH:23]=[C:24]2[C:28](=[C:29]([C:31]([NH2:33])=[O:32])[CH:30]=1)[NH:27][CH:26]=[C:25]2[CH:34]1[CH2:39][CH2:38][N:37]([S:40]([CH2:43][CH3:44])(=[O:42])=[O:41])[CH2:36][CH2:35]1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>O>[CH2:43]([S:40]([N:37]1[CH2:36][CH2:35][CH:34]([C:25]2[C:24]3[C:28](=[C:29]([C:31]([NH2:33])=[O:32])[CH:30]=[C:22]([C:10]4[CH:9]=[N:8][CH:7]=[C:6]([CH2:5][NH:4][CH:2]([CH3:1])[CH3:3])[CH:11]=4)[CH:23]=3)[NH:27][CH:26]=2)[CH2:39][CH2:38]1)(=[O:42])=[O:41])[CH3:44]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamideHCID 57415713N-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl)propan-2-amine

Product 1

HCID 577327213-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-{[(1-methylethyl)amino]methyl}-3-pyridinyl)-1H-indole-7-carboxamideYield 70.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a CEM microwave tube containing (1-methylethyl){[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methyl}amine (22 mg, 0.080 mmol) was added 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (50 mg, 0.121 mmol), K2CO3 (100 mg, 0.724 mmol), dioxane (1.5 mL), H2O (0.5 mL), and chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (7.3 mg, 0.012 mmol). The reaction was heated in a CEM microwave for 30 min at 150° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH), eluting in sequence with H2O (3 mL), MeOH (6 mL) and a 2 M solution of NH3/MeOH (9 mL). The NH3/MeOH fraction was dried under a stream of nitrogen at 50° C. and purified on an Agilent MDAP (Zorbax Eclipse XDB-C18 column: 21.2×100 mm) eluting at 20 mL per min for 1 min with 10% CH3CN/H2O (0.1% TFA) then a linear gradient of 10% CH3CN/H2O (0.1% TFA) to 95% CH3CN/H2O (0.1% TFA) over 8 min and holding at the final concentration for 30 sec. The fractions containing product were filtered through a 2 g Pharmasil CHQAX column (polymer bound ammonium hydroxide; United Chemical Technologies) to remove TFA and concentrated under a stream of nitrogen at 50° C. to give 27.2 mg of the title compound (70%).

Workup

  1. filtrationThe reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH)
  2. washeluting in sequence with H2O (3 mL), MeOH (6 mL)
  3. dry with materialThe NH3/MeOH fraction was dried under a stream of nitrogen at 50° C.
  4. custompurified on an Agilent MDAP (Zorbax Eclipse XDB-C18 column: 21.2×100 mm)
  5. washeluting at 20 mL per min for 1 min with 10% CH3CN/H2O (0.1% TFA)
  6. concentrationconcentration for 30 sec
  7. additionThe fractions containing product
  8. filtrationwere filtered through a 2 g Pharmasil CHQAX column (polymer bound ammonium hydroxide; United Chemical Technologies)
  9. customto remove TFA
  10. concentrationconcentrated under a stream of nitrogen at 50° C.

Sources & evidence

ORD record
ord-cfe4721903d5476999725d63b3431589
Source dataset
uspto-grants-2011_11
Patent number
US08063071B2

Reaction notes

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