Triethylamine → HCID 86707407, compound

HRID 338839Notes

Reaction equation

HRID 338839 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]3[N:16]4[CH:17]=[C:18]([CH:21]([N:26]5[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27]5)[C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:20][C:15]4=[N:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[CH3:39][N:40]1[CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:42]=[N:41]1.C(N(CC)CC)C>CC(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:23][C:22]([F:24])([F:25])[CH:21]([N:26]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27]1)[C:18]1[CH:19]=[CH:20][C:15]2[N:16]([C:12]([C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][C:2]([C:43]5[CH:42]=[N:41][N:40]([CH3:39])[CH:44]=5)=[CH:3][CH:4]=4)[N:9]=3)=[N:13][N:14]=2)[CH:17]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86707406HCID 86707406, compound

Product 1

HCID 86707407HCID 86707407, compoundYield 84.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3776IsopropanolSolvent

Procedure

A solution of tert-butyl (3S)-1-(1-(3-(7-bromo quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (Example 2, Step A; 0.18 g, 0.30 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.127 g, 0.61 mmol), PdCl2(dppf)*dcm (0.0249 g, 0.030 mmol), and triethylamine (0.064 mL, 0.46 mmol) in IPA (3 mL) was heated at 100° C. for 3 hours. After cooling to ambient temperature, the residue was directly purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 10-90% CH3CN/water gradient; 30 CV) to give tert-butyl (3S)-1-(2,2,2-trifluoro-1-(3-(7-(1-methyl-1H-pyrazol-4-yl)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (0.15 g, 83.2%) as a solid.

Workup

  1. customthe residue was directly purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-58a4600ba4344570a89a2c81597196d8
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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