Pyridine → HCID 86590368, compound

HRID 890936Notes

Reaction equation

HRID 890936 reaction equation
[F:1][C:2]1[C:3]([C:22]([OH:24])=[O:23])=[CH:4][C:5]2[C:10](=[O:11])[O:9][CH2:8][N:7]([C:12]3[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=3[CH3:19])[C:6]=2[C:20]=1[F:21].[F:25][C:26]1[C:31](OC(=O)C(F)(F)F)=[C:30]([F:39])[C:29]([F:40])=[C:28]([F:41])[C:27]=1[F:42].N1C=CC=CC=1>CN(C)C=O.C(OCC)(=O)C>[F:25][C:26]1[C:31]([O:23][C:22]([C:3]2[C:2]([F:1])=[C:20]([F:21])[C:6]3[N:7]([C:12]4[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=4[CH3:19])[CH2:8][O:9][C:10](=[O:11])[C:5]=3[CH:4]=2)=[O:24])=[C:30]([F:39])[C:29]([F:40])=[C:28]([F:41])[C:27]=1[F:42]

Participants

6

Reactant 3

HCID 1049PyridineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 22243936HCID 22243936, compound

Product 1

HCID 86590368HCID 86590368, compoundYield 83.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 7,8-difluoro-1-(4-iodo-2-methyl-phenyl)-4-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6-carboxylic acid (0.3 g, 0.67 mmol) in N,N-dimethylformamide (3 mL) is added trifluoroacetic acid pentafluorophenyl ester (0.127 mL, 0.74 mmol) and pyridine (0.60 mL, 0.74 mmol). After stirring for 4 hours the reaction mixture is diluted with ethyl acetate and washed 3 times with 1.0 M HCl solution, 3 times with 5% aqueous NaHCO3 solution, 2 times with water and once with saturated brine solution. The organic layers were collected and dried over Na2SO4, filtered and concentrated in vacuo affording 7,8-difluoro-1-(4-iodo-2-methyl-phenyl)-4-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6-carboxylic acid pentafluorophenylester as a dark orange oil (0.34 g, 83.1%). To a suspension of 7,8-difluoro-1-(4-iodo-2-methyl-phenyl)-4-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6-carboxylic acid pentafluorophenylester (0.33 g, 0.54 mmol) in freshly distilled THF (10 mL) is added methylamine hydrochloride (0.037 g, 0.54 mmol) and N,N-diisopropylethylamine (0.019 mL, 1.08 mmol). After stirring for 17 hours, the reaction mixture was diluted with ethyl acetate and washed 2 times with water and 2 times with saturated brine solution. The organic layers were collected and dried over Na2SO4, filtered and concentrated in vacuo affording 7,8-difluoro-1-(4-iodo-2-methyl-phenyl)-4-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6-carboxylic acid methylamide as a yellow solid (0.19 g, 76.9%); mp 219–223° C.; 1NMR (400 MHz; DMSO-d6) 8.40 (s, 1H), 8.06 (d, 1H, J=6.8), 7.74 (s, 1H), 7.50 (d, 1H, J=8.4), 6.87 (d, 1H, J=8.0), 5.61 (s, 2H), 2.76 (d, 3H, J=4.4), 2.25 (s, 3H); MS(APCI)m+1=459; Anal.calcd/found for C17H13F2IN2O3 C 45.00/45.39, H 3.01/3.16, N 6.05/5.88.

Workup

  1. washwashed 3 times with 1.0 M HCl solution, 3 times with 5% aqueous NaHCO3 solution, 2 times with water
  2. customThe organic layers were collected
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26332c8c7cfa449bbbf0aa51d4a9da50
Source dataset
uspto-grants-2006_02
Patent number
US07001905B2

Reaction notes

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