Dichloromethane → HCID 11503305, compound

HRID 899146Notes

Reaction equation

[CH2:1]([N:8]1[CH2:15][CH:14]2[O:16][CH:10]([CH2:11][NH:12][CH2:13]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]([C:19]1[CH:44]=[CH:43][C:22]([O:23][CH2:24][CH2:25][N:26]([CH2:30][CH2:31]OS(C2C=CC(C)=CC=2)(=O)=O)[C:27]([NH2:29])=[O:28])=[CH:21][CH:20]=1)#[N:18].C(Cl)Cl>C(#N)C>[CH2:1]([N:8]1[CH2:15][CH:14]2[O:16][CH:10]([CH2:11][N:12]([CH2:31][CH2:30][N:26]([CH2:25][CH2:24][O:23][C:22]3[CH:21]=[CH:20][C:19]([C:17]#[N:18])=[CH:44][CH:43]=3)[C:27]([NH2:29])=[O:28])[CH2:13]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

3-Benzyl-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane (0.18 g, 0.82 mmol; see WO 01/28992) and toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-ureido}ethyl ester (0.50 g, 1.24 mmol; see Preparation D above) were mixed in dry acetonitrile (15 mL) and stirred at 60° C. overnight. DCM (10 mL) was added, together with 0.5 g of PS—NCO (polymer-supported isocyanate). The mixture was stirred for 2 h, then filtered and evaporated. The crude product was put on a SCX-II (cation exchanger)-plug, which plug was then eluted with DCM:MeOH (NH3-saturated), 80:20. The product was further purified on a Horizon prep. column (40 g, A: DCM(1% MeOH), B: DCM/MeOH(NH3-sat.), 80:20. Gradient 0-30% B over 1080 mL). The product was then further purified by prep. HPLC and finally extracted with DCM/Na2CO3 (aq.) to give 193 mg (51.9%) of the title compound.

Workup

stirringThe mixture was stirred for 2 h
filtrationfiltered
customevaporated
washwas then eluted with DCM
customThe product was further purified on a Horizon prep
customThe product was then further purified by prep
extractionHPLC and finally extracted with DCM/Na2CO3 (aq.)

Sources & evidence

ORD record: ord-b2feadb2ce3f4958ad063397c84e585b
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07354917B2

Reaction notes

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