Ethyl isocyanatoacetate → {3-[4-(2,4-Dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-ureido}-acetic acid ethyl ester

HRID 1663168Notes

Reaction equation

HRID 1663168 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.[CH2:21]([O:23][C:24](=[O:29])[CH2:25][N:26]=[C:27]=[O:28])[CH3:22]>N1C=CC=CC=1>[CH2:21]([O:23][C:24](=[O:29])[CH2:25][NH:26][C:27]([NH: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)=[O:28])[CH3:22]

Participants

4

Reactant 2

HCID 76283Ethyl isocyanatoacetateHCID 583773961-(2-Amino-pyridin-4-ylmethyl)-1H-benzo[d][1,3]oxazine-2,4-dione

Product 1

HCID 86615648{3-[4-(2,4-Dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-ureido}-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

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.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. customevaporated under reduced pressure
  6. additionThe resulting oil was treated with EtOAc (3 ml)
  7. customgave a precipitate that
  8. customwas isolated by filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-88f77966dab744fe87a876ff2f068461
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

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