Cesium carbonate → 6-Chloro-8-cyclopropyl-5-methyl-2-[2-(2-methyl-5-pyrrolidin-1-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyridine

HRID 1055006Notes

Reaction equation

Br[C:2]1[C:3]2[N:4]([N:10]=[C:11]([CH2:13][CH2:14][C:15]3[N:16]([CH3:25])[N:17]=[C:18]([N:20]4[CH2:24][CH2:23][CH2:22][CH2:21]4)[N:19]=3)[N:12]=2)[C:5]([CH3:9])=[C:6]([Cl:8])[CH:7]=1.[CH:26]1(B(O)O)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:8][C:6]1[CH:7]=[C:2]([CH:26]2[CH2:28][CH2:27]2)[C:3]2[N:4]([N:10]=[C:11]([CH2:13][CH2:14][C:15]3[N:16]([CH3:25])[N:17]=[C:18]([N:20]4[CH2:24][CH2:23][CH2:22][CH2:21]4)[N:19]=3)[N:12]=2)[C:5]=1[CH3:9]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 8-bromo-6-chloro-5-methyl-2-[2-(2-methyl-5-pyrrolidin-1-yl-2H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 70.6 μmol, Eq: 1), cyclopropyl-boronic acid (9.1 mg, 106 μmol, Eq: 1.5) and cesium carbonate (46.0 mg, 141 μmol, Eq: 2) in dioxane (0.75 mL) and water (0.075 ml) was stirred for 4 min. Dichloro1,1′-bis(diphenylphosphino)ferrocene palladium(II) (11.6 mg, 14.2 μmol, 0.2 Eq) was added, and the mixture was heated at 100° C. for 30 min in a microwave oven. The mixture was separated by preparative HPLC to give the desired product (6.2 mg, 22%) as a white solid. MS: m/z=386.4 (M+H+)

Workup

customThe mixture was separated by preparative HPLC

Sources & evidence

ORD record: ord-cd5ee708ce834d9e939b32ac8a06db10
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394311B2

Reaction notes

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