Potassium Carbonate → N-Cyclopropyl-4-[8-(methylsulfanyl)-6-phenylimidazo[1,2-a]pyrazin-3-yl]benzamide

HRID 925593Notes

Reaction equation

HRID 925593 reaction equation
Br[C:2]1[N:3]=[C:4]([S:23][CH3:24])[C:5]2[N:6]([C:8]([C:11]3[CH:22]=[CH:21][C:14]([C:15]([NH:17][CH:18]4[CH2:20][CH2:19]4)=[O:16])=[CH:13][CH:12]=3)=[CH:9][N:10]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(O)CC.CN1C(=O)CCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:18]1([NH:17][C:15](=[O:16])[C:14]2[CH:21]=[CH:22][C:11]([C:8]3[N:6]4[CH:7]=[C:2]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[N:3]=[C:4]([S:23][CH3:24])[C:5]4=[N:10][CH:9]=3)=[CH:12][CH:13]=2)[CH2:20][CH2:19]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 533898994-[6-Bromo-8-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylbenzamide

Product 1

HCID 53389900N-Cyclopropyl-4-[8-(methylsulfanyl)-6-phenylimidazo[1,2-a]pyrazin-3-yl]benzamideYield 80.5%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 10311-PropanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 4-(6-bromo-8-methylsulfanyl-imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropyl-benzamide (7.34 g, 18.2 mmol) in n-propanol (270 mL) and NMP (15 mL) was subsequently added 27.3 mL 2M potassium carbonate solution, 4.44 g phenylboronic acid (36.4 mmol, 2 eq), triphenylphosphine (238.7 mg, 0.91 mmol, 0.05 eq), 1.28 g bis(triphenylphosphin)palladium(II)chloride (1.82 mmol, 0.1 eq) in one portion at rt under argon atmosphere. After stirring for 2 h at 120° C., the mixture was concentrated in vaccuo (50% v/v), triturated with water and extracted with DCM. The organic phase was dried over sodium sulphate, filtered and the solvent was evaporated. Purification by flash chromatography (ethyl acetate/n-hexane) followed by crystallization from ethyl acetate yielded 5.87 g (80.5%)N-Cyclopropyl-4-(8-methylsulfanyl-6-phenyl-imidazo[1,2-a]pyrazin-3-yl)-benzamide: 1H-NMR (300 MHz, CDCl3): δ=8.30 (1H, s), 7.94 (4H, d), 7.77 (1H, s), 7.65 (2H, d), 7.50-7.37 (3H, m), 6.38 (1H, bs), 2.95 (1H, m), 2.80 (3H, s), 1.04 (6H, d), 0.92 (2H, m), 0.67 (2H, m) ppm.

Workup

  1. customat rt
  2. concentrationthe mixture was concentrated in vaccuo (50% v/v),
  3. customtriturated with water
  4. extractionextracted with DCM
  5. dry with materialThe organic phase was dried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customPurification by flash chromatography (ethyl acetate/n-hexane)
  9. customfollowed by crystallization from ethyl acetate

Sources & evidence

ORD record
ord-a6e9224dd2f3497a83a0a649e4064504
Source dataset
uspto-grants-2016_03
Patent number
US09284317B2

Reaction notes

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