Sodium t-butoxide → 2-Fluoro-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-benzamide

HRID 1011274Notes

Reaction equation

HRID 1011274 reaction equation
Cl[C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[CH:31][C:27]=1[C:28]([NH2:30])=[O:29].CC([O-])(C)C.[Na+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:26]1[CH:34]=[C:33]([C:2]2[N:7]3[N:8]=[CH:9][N:10]=[C:6]3[C:5]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]4)=[CH:14][CH:13]=3)=[CH:4][CH:3]=2)[CH:32]=[CH:31][C:27]=1[C:28]([NH2:30])=[O:29]

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 57664356(5-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amineHCID 590230642-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 249471892-Fluoro-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-benzamideYield 18.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

A suspension of (5-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (50 mg, 146 μmol), 2-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (97 mg, 360 μmol), Pd(PPh3)4 (51 mg, 40 μmol) and NaOtBu (56 mg, 580 μmol) in 1.2 mL of DMF/water (5:1, degassed) is degassed for 1 min in a sealed tube. The tube is sealed and the reaction mixture heated at 110° C. for forty minutes in the microwave (CEM explorer) and then at the same temperature for thirty minutes in an oil bath. After evaporation of the solvents the residue is taken up in dichloromethane, filtered and evaporated. The crude product is purified by flash chromatography (silica gel, dichloromethane/7N NH3 in methanol 97:3 to 90:10) and triturated (3× with ethyl acetate) affording the title compound (12 mg) as a solid.

Workup

  1. customis degassed for 1 min in a sealed tube
  2. customThe tube is sealed
  3. waitat the same temperature for thirty minutes in an oil bath
  4. customAfter evaporation of the solvents the residue
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product is purified by flash chromatography (silica gel, dichloromethane/7N NH3 in methanol 97:3 to 90:10)
  8. customtriturated (3× with ethyl acetate)

Sources & evidence

ORD record
ord-9e75ba36a0d04ea4a5777e086fbeeb1e
Source dataset
uspto-grants-2011_07
Patent number
US07977352B2

Reaction notes

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