Potassium Phosphate, Tribasic → 4-[4-(7-Pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramide

HRID 1446754Notes

Reaction equation

HRID 1446754 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][C:20]([NH:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)=[O:21])=[CH:13][CH:12]=3)=[CH:9][N:10]=[C:4]2[CH:3]=1.[N:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.ClCCl.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].O1CCOCC1>[N:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]4[CH:12]=[CH:13][C:14]([CH2:17][CH2:18][CH2:19][C:20]([NH:22][C:23]5[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=5)=[O:21])=[CH:15][CH:16]=4)=[CH:9][N:10]=[C:4]3[CH:3]=2)=[CH:35][CH:34]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 685428324-[4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramide

Product 1

HCID 578634214-[4-(7-Pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramideYield 59.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
102.5 °C

Procedure

Combine 4-[4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramide (0.15 g, 0.32 mmol), 4-pyridine boronic acid (0.04 g, 0.35 mmol), S-Phos (0.02 g, 0.04 mmol) and K3PO4 (0.13 g, 0.63 mmol) with dioxane (3.5 mL) and water (1.5 mL) and stir at room temperature while the reaction contents are de-gassed with nitrogen for 5 minutes. Add palladium diacetate (0.01 g, 0.04 mmol). Heat to 100-105° C. for 20 hours. Cool and dilute with water (10 mL) and dichloromethane. The organic layer are then filtered onto a pre-equilibrated in methanol Varian SCX column (10 g), washed with 30 mL each of water, methanol, dichloromethane and methanol. Elute crude product with 2N methanolic ammonia (50 mL). Concentrate the ammonia solution in vacuo to dryness to yield a residue that is chromatographed on silica (0→3% methanol in ethyl acetate over 30 min) to yield 4-[4-(7-Pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramide (0.10 g, 0.19 mmol). MS(ESI), m/z 501 (M+1).

Workup

  1. customare de-gassed with nitrogen for 5 minutes
  2. temperatureCool
  3. filtrationThe organic layer are then filtered onto a pre-equilibrated in methanol Varian SCX column (10 g)
  4. washwashed with 30 mL each of water, methanol, dichloromethane and methanol
  5. washElute crude product with 2N methanolic ammonia (50 mL)
  6. concentrationConcentrate the ammonia solution in vacuo to dryness
  7. customto yield a residue that
  8. customis chromatographed on silica (0→3% methanol in ethyl acetate over 30 min)

Sources & evidence

ORD record
ord-6dbdf7fdc5ca4609a26e725543c3c9d4
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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