tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylate → HCID 49839495, compound

HRID 1890032Notes

Reaction equation

HRID 1890032 reaction equation
BrC1C2N(N=C(Cl)N=2)C=CC=1.ClC1N=C2C(B(O)O)=CC=CN2N=1.[Cl:25][C:26]1[N:42]=[C:29]2[C:30]([C:34]3[CH:39]=[N:38][C:37]([O:40][CH3:41])=[CH:36][N:35]=3)=[CH:31][CH:32]=[CH:33][N:28]2[N:27]=1.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([C:56]2[CH:61]=[CH:60][C:59]([NH2:62])=[CH:58][CH:57]=2)[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[Cl:25][C:26]1[N:42]=[C:29]2[C:30]([C:34]3[CH:39]=[N:38][C:37]([O:40][CH3:41])=[CH:36][N:35]=3)=[CH:31][CH:32]=[CH:33][N:28]2[N:27]=1.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([C:56]2[CH:61]=[CH:60][C:59]([NH:62][C:26]3[N:42]=[C:29]4[C:30]([C:34]5[CH:39]=[N:38][C:37]([O:40][CH3:41])=[CH:36][N:35]=5)=[CH:31][CH:32]=[CH:33][N:28]4[N:27]=3)=[CH:58][CH:57]=2)[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

7

Reactant 5

HCID 21940085tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylateHCID 249469872,2'-Bis(dicyclohexylphosphino)-1,1'-biphenylHCID 674813708-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridineHCID 67481400HCID 67481400, compoundHCID 67481435HCID 67481435, compound

Product 2

HCID 49839495HCID 49839495, compoundHCID 67481435HCID 67481435, compound

Procedure

A solution of 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.29 g, 1.25 mmol) in anhydrous tetrahydrofuran (6.0 mL) was cooled to −78° C. under nitrogen as n-butyllithium (2N in tetrahydrofuran, 1.87 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 minutes then trimethylboronate (0.213 mL, 1.87 mmol) was added, and the reaction was slowly warmed and stirred at room temperature for 2 hours. Hydrochloric acid solution (2N, 2 mL) was added and the reaction was stirred for 1 hour then extracted with dichloromethane, combined, and concentrated. The crude was triturated with ether to give 2-chloro-[1,2,4]triazolo[1,5-a]pyridine-8-boronic acid (0.174 g, 69%). MP=227-229° C. MS=198 (MH)+. 284b) 2-Chloro-8-(5-methoxy-pyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyridine was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine and 2-chloro-[1,2,4]triazolo[1,5-a]pyridine-8-boronic acid in a manner analogous to Example 2c (0.115 g, 51%). %). MP=210° C. (dec.). MS=262 (MH)+. 284c) 4-{4-[8-(5-Methoxy-pyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester was prepared from 2-chloro-8-(5-methoxy-pyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyridine 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 (0.039 g, 19%). MP=193-195° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.75 (s, 1H), 9.69 (s, 1H), 8.87 (d, 1H), 8.49 (m, 1H), 8.35 (m, 1H), 7.65 (m, 2H), 7.20 (m, 3H), 4.08 (m, 2H), 4.02 (s, 3H), 2.80 (m, 2H), 2.62 (m, 1H), 1.72 (m, 2H), 1.51 (m, 2H), 1.40 (s, 9H). MS=502 (MH)+.

Sources & evidence

ORD record
ord-da70359b031f45409f1847d7caa09323
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

Loading…