Potassium Carbonate → 7-(2-{1-[2-(4-Cyanophenoxy)ethyl]ureido}ethyl)-9-oxa-3,7-diazabicyclo-[3.3.1]nonane-3-carboxylic acid tert-butyl ester

HRID 899125Notes

Reaction equation

[C:1]([C:3]1[CH:28]=[CH:27][C:6]([O:7][CH2:8][CH2:9][N:10]([CH2:14][CH2:15]OS(C2C=CC(C)=CC=2)(=O)=O)[C:11]([NH2:13])=[O:12])=[CH:5][CH:4]=1)#[N:2].[C:29]([O:33][C:34]([N:36]1[CH2:43][CH:42]2[O:44][CH:38]([CH2:39][NH:40][CH2:41]2)[CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C([O-])([O-])=O.[K+].[K+].[Br-].[Li+]>C(#N)C>[C:29]([O:33][C:34]([N:36]1[CH2:37][CH:38]2[O:44][CH:42]([CH2:41][N:40]([CH2:15][CH2:14][N:10]([CH2:9][CH2:8][O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:28][CH:27]=3)[C:11]([NH2:13])=[O:12])[CH2:39]2)[CH2:43]1)=[O:35])([CH3:32])([CH3:30])[CH3:31]

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-ureido}ethyl ester (15 g, 0.0372 mol, 1.0 eq.; see Preparation D above), 9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (8.525 g, 0.0372 mol, 1.0 eq.; see WO 01/28992), fused K2CO3 (7.7 g, 0.0558 mol, 1.5 eq.) and lithium bromide (9.6 g, 0.1116 mol, 3.0 eq.) in dry acetonitrile (350 mL) was heated to 40° C. under N2 for 4 days. The reaction was cooled to rt, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography over silica gel, using 3% methanol and DCM as eluent, to yield the sub-title compound as a white solid. Yield: 7 g, 40.9%.

Workup

temperatureThe reaction was cooled to rt
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure
customThe resulting residue was purified by column chromatography over silica gel

Sources & evidence

ORD record: ord-c71c1595f5084081b31806ce941006da
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07354917B2

Reaction notes

Loading…