Cesium carbonate → Tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

HRID 873560Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([C:5]([NH:7][C:8]2[CH:27]=[CH:26][C:11]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)=[CH:10][CH:9]=2)=[O:6])[CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[N:37]1[CH:38]=[CH:39][CH:40]=[C:35]([N:1]2[CH2:4][CH:3]([C:5]([NH:7][C:8]3[CH:9]=[CH:10][C:11]([O:12][CH:13]4[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[CH2:17][CH2:18]4)=[CH:26][CH:27]=3)=[O:6])[CH2:2]2)[CH:36]=1

Participants

Conditions

Temperature: 100 °C

Procedure

tert-Butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate (4.97 g, 13.24 mmol), cesium carbonate (10.78 g, 33.1 mmol), 3-bromopyridine (1.307 ml, 13.24 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.764 g, 1.32 mmol) and bis(dibenzylideneacetone)palladium(0) (0.606 g, 0.662 mmol) were suspended in dioxane (50 ml), bubbled with nitrogen for 30 minutes and heated at 100° C. overnight. The mixture was filtered through a celite pad with dichloromethane washes and the filtrate was concentrated. Normal phase chromatography provided the title compound.

Workup

custombubbled with nitrogen for 30 minutes
filtrationThe mixture was filtered through a celite pad with dichloromethane washes
concentrationthe filtrate was concentrated

Sources & evidence

ORD record: ord-febb9303495c416daa1e382b7ce2c550
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975398B2

Reaction notes

Loading…