Tetrahydrofuran → HCID 23598831, compound

HRID 890937Notes

Reaction equation

HRID 890937 reaction equation
FC1C([O:8][C:9]([C:11]2[C:29]([F:30])=[C:28]([F:31])[C:14]3[N:15]([C:20]4[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=4[CH3:27])[CH2:16][O:17][C:18](=[O:19])[C:13]=3[CH:12]=2)=O)=C(F)C(F)=C(F)C=1F.C1COCC1.Cl.CN.[CH:44]([N:47](CC)C(C)C)(C)C>C(OCC)(=O)C>[CH3:44][NH:47][C:9]([C:11]1[C:29]([F:30])=[C:28]([F:31])[C:14]2[N:15]([C:20]3[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=3[CH3:27])[CH2:16][O:17][C:18](=[O:19])[C:13]=2[CH:12]=1)=[O:8]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 86590368HCID 86590368, compound

Product 1

HCID 23598831HCID 23598831, compoundYield 76.9%

Reagents, catalysts & solvents 1

HCID 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 2 times with water and 2 times with saturated brine solution
  2. customThe organic layers were collected
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-afdda7260ced459eb376e52a57882e69
Source dataset
uspto-grants-2006_02
Patent number
US07001905B2

Reaction notes

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