Potassium Phosphate, Tribasic → N-{4-[7-(4-Methanesulfonyl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-benzyl}-2-(m-trifluoromethyl-phenyl)-acetamide

HRID 1446762Notes

Reaction equation

HRID 1446762 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:31]=[CH:30][C:14]([CH2:15][NH:16][C:17](=[O:29])[CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)=[CH:13][CH:12]=3)=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:32][S:33]([C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)(=[O:35])=[O:34].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1.O>[CH3:32][S:33]([C:36]1[CH:41]=[CH:40][C:39]([C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]4[CH:12]=[CH:13][C:14]([CH2:15][NH:16][C:17](=[O:29])[CH2:18][C:19]5[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:26])[F:27])[CH:20]=5)=[CH:30][CH:31]=4)=[CH:9][N:10]=[C:4]3[CH:3]=2)=[CH:38][CH:37]=1)(=[O:35])=[O:34]

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 68543017N-[4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-benzyl]-2-(m-trifluoromethyl-phenyl)-acetamide

Product 1

HCID 57863465N-{4-[7-(4-Methanesulfonyl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-benzyl}-2-(m-trifluoromethyl-phenyl)-acetamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
45 °C

Procedure

In a 12 mL septum capped vial purged with N2 add N-[4-(7-chloro-imidazo[1,2-a]pyridin-3-yl)-benzyl]-2-(m-trifluoromethyl-phenyl)-acetamide (144 mg, 0.32 mmol), 4-(methylsulfonyl)phenyl boronic acid (89 mg, 0.44 mmols), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (23.6 mg) [X-Phos is alternatively used as the ligand in this reaction], Pd(OAc)2 (6 mg), K3PO4 (218 mg, 1.02 mmol), 1,4-dioxane: H2O 2:1 (5 mL). Deoxygenate the vial again with N2 then heat to 45° C. for 24 hours. Cool the reaction and transfer to a separatory funnel and discard the bottom aqueous layer. Evaporate the solvents under vacuum and take up the residue into CH2Cl2 with a trace of MeOH. Chromatograph the crude reaction on SiO2 eluting with a gradient of 0% to 8% of 2 M NH3 in MeOH with the balance CH2Cl2 Dry the product in a vacuum oven at 40° C. for 24 hours to give 38.6 mg (21%) MS (ES), m/z 564.3 (M+1).

Workup

  1. custompurged with N2
  2. customDeoxygenate the vial again with N2
  3. temperatureCool
  4. customthe reaction and transfer to a separatory funnel
  5. customEvaporate the solvents under vacuum
  6. customChromatograph the crude reaction on SiO2 eluting with a gradient of 0% to 8% of 2 M NH3 in MeOH with the balance CH2Cl2
  7. customDry the product in a vacuum oven at 40° C. for 24 hours
  8. customto give 38.6 mg (21%)

Sources & evidence

ORD record
ord-3abffa252f8340cba3b8699aa9f599eb
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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