Methyl Isocyanate → 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-3-methyl-urea

HRID 1663167Notes

Reaction equation

HRID 1663167 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.[N:21]([CH3:24])=[C:22]=[O: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:22]([NH:21][CH3:24])=[O: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 12228Methyl Isocyanate2×HCID 583773961-(2-Amino-pyridin-4-ylmethyl)-1H-benzo[d][1,3]oxazine-2,4-dione

Product 1

HCID 445157491-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-3-methyl-urea

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 (7.0 g, see preparation 7b) in pyridine (70 ml) was added isocyanatomethane (5 eq.) over 45 minutes. More isocyanatomethane (in total 20 eq.) was added over time until all starting material had been consumed. The solvent was evaporated under reduced pressure. The remaining solid material washed with EtOAc (50 ml) and gave 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)-pyridin-2-yl]-3-methyl-urea after drying in vacuo. 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 167.4, 155.3, 153.7, 151.2, 148.5, 146.6, 141.8, 132.6, 132.2, 129.2, 128.0, 118.7, 115.1, 114.7, 112.9, 111.5, 110.8, 109.1, 76.0, 45.2, 25.8.

Workup

  1. customhad been consumed
  2. customThe solvent was evaporated under reduced pressure
  3. washThe remaining solid material washed with EtOAc (50 ml)

Sources & evidence

ORD record
ord-6895ea8fb1e64103aedeb7bbc39fc8df
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

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