Cesium carbonate → tert-Butyl 4-(5-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

HRID 592440Notes

Reaction equation

HRID 592440 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([CH3:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[CH:26][C:27]([CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[N:28][CH:29]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:19]([C:16]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:6]2[C:5]([CH3:22])=[CH:4][N:3]=[C:2]([NH:23][C:24]3[CH:25]=[CH:26][C:27]([CH:30]4[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]4)=[N:28][CH:29]=3)[N:7]=2)[CH2:18][CH2:17]1)(=[O:20])[NH2:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59128562tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylateHCID 867123151-(2-(2-(2-Chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 86712319tert-Butyl 4-(5-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A40 (0.240 g, 0.761 mmol), tert-butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate (0.422 g, 1.52 mmol), Pd(OAc)2 (0.003 g, 0.015 mmol), Xantphos (0.018 g, 0.030 mmol) and Cs2CO3 (0.744 g, 2.28 mmol) in dioxane (8 mL) was bubbled with N2 for 10 minutes and then stirred in the microwave at 120° C. for 20 minutes. The volatiles were removed in vacuo and the residue was adsorbed onto SiO2 and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-20% MeOH in EtOAc) to give the title compound A45 as a white solid (0.212 g, 50%). LCMS-D: rt 3.20 min; m/z 557 [M+H]+.

Workup

  1. customwas bubbled with N2 for 10 minutes
  2. customThe volatiles were removed in vacuo
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-117e923ddd6146978b2ca1d8abb19957
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

Loading…