Cesium carbonate → Methyl 4-(8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)benzoate

HRID 57764Notes

Reaction equation

HRID 57764 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH2:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1.I[C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[F:20][C:2]([F:19])([F:1])[C:3]1[CH:4]=[C:5]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH:18][C:22]4[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=4)[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 69273Methyl 4-iodobenzoateHCID 591990748-(3-Trifluoromethylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

Product 1

HCID 44554495Methyl 4-(8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)benzoateYield 72.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (1.0 g, 3.6 mmol, 1 equiv), methyl 4-iodobenzoate (0.95 g, 3.6 mmol, 1.0 equiv), palladium (II) acetate (0.080 g, 0.36 mmol, 0.10 equiv), cesium carbonate (2.34 g, 7.18 mmol, 2.0 equiv), and Xantphos (0.10 g, 0.17 mmol, 0.047 equiv) in 1,4-dioxane (20 mL) was heated to 80° C. After 16 h, the reaction mixture was concentrated in vacuo, and the resulting residue was diluted with methanol and water. The solid was collected by filtration and rinsed sequentially with water, isopropanol, and hexanes to afford crude methyl 4-(8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)benzoate (1.07 g, 72%). LCMS (ESI) m/z: 413.0; 1H NMR (400 MHz, DMSO-d6) δ: 10.29 (s, 1H), 8.88 (m, 1H), 8.63 (s, 1H), 8.40 (m, 1H), 8.02 (m, 1H), 7.78-7.90 (m, 6H), 7.20 (m, 1H), 3.80 (s, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additionthe resulting residue was diluted with methanol and water
  3. filtrationThe solid was collected by filtration
  4. washrinsed sequentially with water, isopropanol, and hexanes

Sources & evidence

ORD record
ord-75560ac2175a4fdda25280f337f9e548
Source dataset
uspto-grants-2016_09
Patent number
US09434732B2

Reaction notes

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