4-[(Aminooxy)methyl]benzonitrile hydrochloride → [3-(4-{[2-(4-Cyano-benzyloxycarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-ureido]-acetic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[C:14]([CH2:16][N:17]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[C:20](=[O:27])OC2=O)[CH:13]=[CH:12][N:11]=1)=[O:8])[CH3:2].Cl.[C:31]([C:33]1[CH:41]=[CH:40][C:36]([CH2:37][O:38][NH2:39])=[CH:35][CH:34]=1)#[N:32]>>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[C:14]([CH2:16][NH:17][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[C:20](=[O:27])[NH:39][O:38][CH2:37][C:36]2[CH:40]=[CH:41][C:33]([C:31]#[N:32])=[CH:34][CH:35]=2)[CH:13]=[CH:12][N:11]=1)=[O:8])[CH3:2]Participants
Reactant 2
Product 1
Procedure
To a stirred solution of 1-(2-amino-pyridin-4-ylmethyl)-1H-benzo[d][1,3]oxazine-2,4-dione (600 mg, see preparation 7b) in pyridine (7 ml) was added isocyanato-acetic acid ethyl ester (0.4 ml). The reaction mixture was stirred at room temperature for 3 hours, and the solvent was evaporated under reduced pressure. The residue was dissolved in EtOAc and washed with water and brine. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The resulting oil was treated with EtOAc (3 ml) and gave a precipitate that was isolated by filtration and dried in vacuo, affording {3-[4-(2,4-Dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-ureido}-acetic acid ethyl ester (0.53 g). Step 2: This anhydride intermediate was converted into the title compound by reaction with O-(4-cyanobenzyl)hydroxylamine hydrochloride (see preparation 10), using general procedure 1A. 13C-NMR (DMSO-d6) δ 170.3, 167.4, 154.8, 153.5, 151.4, 148.5, 146.7, 141.8, 132.7, 132.2, 129.1, 128.0, 118.6, 115.4, 114.8, 112.9, 111.5, 110.7, 109.3, 76.0, 60.3, 45.2, 41.2, 14.0.
Sources & evidence
- ORD record
- ord-d6833c7ab34d409d8d3839779e96db9d
- Source dataset
- uspto-grants-2011_10
- Patent number
- US08034811B2
Reaction notes
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