tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylate → 4-{4-[8-(4-Acetylamino-phenylsulfanyl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1890031Notes

Reaction equation

HRID 1890031 reaction equation
Cl[C:2]1[N:21]=[C:5]2[C:6]([S:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:20])[CH3:19])=[CH:13][CH:12]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([C:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:2]3[N:21]=[C:5]4[C:6]([S:10][C:11]5[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:20])[CH3:19])=[CH:13][CH:12]=5)=[CH:7][CH:8]=[CH:9][N:4]4[N:3]=3)=[CH:37][CH:36]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

4

Reactant 3

HCID 21940085tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylateHCID 249469872,2'-Bis(dicyclohexylphosphino)-1,1'-biphenylHCID 67479086N-[4-(2-chloro-[1,2,4]triazolo[1,5-a]pyridine-8-ylsulfanyl)-phenyl]acetamide

Product 1

HCID 498394934-{4-[8-(4-Acetylamino-phenylsulfanyl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

Procedure

A solution of 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.47 g, 2.00 mmol) in dioxane (6.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (0.256 g, 0.28 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.324 g, 0.56 mmol), N,N-disopropylethylamine (0.52 g, 4.00 mmol), and acetamidothiophenol (0.37 g, 2.20 mmol) under nitrogen. The mixture was degassed with nitrogen for 3 minutes, and then heated to 100° C. for 14 hours. The reaction was cooled to room temperature, filtered through diatomaceous earth, washed with dichloromethane, and concentrated. The residue was diluted with dichloromethane, washed with brine, dried over sodium sulfate, and concentrated. The crude was purified by flash chromatography (silica gel hexane to 5% methanol in dichloromethane) to give N-[4-(2-chloro-[1,2,4]triazolo[1,5-a]pyridine-8-ylsulfanyl)-phenyl]acetamide (0.51 g, 80%). MP=148-150° C. MS=319 (MH)+. 281b) 4-{4-[8-(4-Acetylamino-phenylsulfanyl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester was prepared from N-[4-(2-chloro-[1,2,4]triazolo[1,5-a]pyridine-8-ylsulfanyl)-phenyl]acetamide and 4-(4-amino-phenyl)-piperidine-1-carboxylic acid tert-butyl ester with 2,2′-bis-dicyclohexylphosphanyl-biphenyl as the ligand in a manner analogous to Example 2d (0.023 g, 10%). MP=226-228° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.2 (s, 1H), 9.69 (s, 1H), 8.62 (d, 1H), 7.72 (m, 2H), 7.55 (m, 2H), 7.49 (m, 2H), 7.12 (m, 2H), 6.91 (m, 1H), 4.18 (bs, 2H), 2.78 (bs, 2H), 2.58 (m, 1H), 2.04 (s, 3H), 1.66 (m, 2H), 1.51 (m, 2H), 1.42 (s, 9H). MS=559 (MH)+.

Sources & evidence

ORD record
ord-ded4312a72ed4043a570b83372449911
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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