2-Isocyanatoethyl methacrylate → 2-methyl-acrylic acid 2-{3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-ureido}-ethyl ester

HRID 1663171Notes

Reaction equation

HRID 1663171 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12](=[O:19])[O:11][C:10]2=[O:20])[CH:5]=[CH:4][N:3]=1.[C:21]([O:26][CH2:27][CH2:28][N:29]=[C:30]=[O:31])(=[O:25])[C:22]([CH3:24])=[CH2:23]>N1C=CC=CC=1>[O:20]=[C:10]1[N:9]([CH2:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:30](=[O:31])[NH:29][CH2:28][CH2:27][O:26][C:21](=[O:25])[C:22]([CH3:24])=[CH2:23])[CH:7]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12](=[O:19])[O:11]1

Participants

4

Reactant 2

HCID 354092-Isocyanatoethyl methacrylate2×HCID 583773961-(2-Amino-pyridin-4-ylmethyl)-1H-benzo[d][1,3]oxazine-2,4-dione

Product 1

HCID 866156492-methyl-acrylic acid 2-{3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-ureido}-ethyl ester

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 1-(2-amino-pyridin-4-ylmethyl)-1H-benzo[d][1,3]oxazine-2,4-dione (1.2 g, see preparation 7b) in pyridine was added isocyanatoethyl methacrylate (0.76 ml). The reaction mixture was heated to 40° C. and stirred for 2 hours. More isocyanatoethyl methacrylate (0.1 ml) was added and stirring was continued for 2 hours. The solvent was evaporated under reduced pressure and EtOAc (10 ml) was added to the residue. On scraping a solid material formed, that was isolated by filtration and dried in vacuo, affording 2-methyl-acrylic acid 2-{3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-ureido}-ethyl ester (1.78 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 167.5, 166.5, 154.8, 153.7, 151.4, 148.6, 146.6, 141.9, 135.8, 132.8, 132.3, 129.2, 128.1, 125.9, 118.8, 115.4, 114.9, 113.0, 111.6, 110.9, 109.4, 76.1, 63.7, 45.4, 38.0, 18.0.

Workup

  1. stirringstirring
  2. waitwas continued for 2 hours
  3. customThe solvent was evaporated under reduced pressure and EtOAc (10 ml)
  4. additionwas added to the residue
  5. customformed
  6. customthat was isolated by filtration
  7. customdried in vacuo

Sources & evidence

ORD record
ord-faee35986b79419ba944b692d580bd61
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

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