Pyridine → HCID 86590369, compound

HRID 890939Notes

Reaction equation

HRID 890939 reaction equation
[F:1][C:2]1[C:10]([F:11])=[C:9]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[CH3:20])[C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[C:21]([NH:23][CH3:24])=[O:22].[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:7][C:6](=[O:8])[C:5]2[C:9]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=3[CH3:20])=[C:10]([F:11])[C:2]([F:1])=[C:3]([C:21]([NH:23][CH3:24])=[O:22])[CH:4]=2)=[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 22243979HCID 22243979, compound

Product 1

HCID 86590369HCID 86590369, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4,5-difluoro-6-(-4-iodo-2-methyl-phenylamino)-N-methyl-isophthalamic acid (0.13 g, 0.29 mmol) in N,N-dimethylformamide (5 mL) is added trifluoroacetic acid pentafluorophenyl ester (0.055 mL, 0.32 mmol) and pyridine (0.03 mL, 0.32 mmol). After stirring for 17 hours the reaction mixture is diluted with ethyl acetate and transferred to a separatory funnel, washed twice with 1.0 M HCl, twice 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 4,5-difluoro-6-(4-iodo-2-methyl-phenylamino)-N-methyl-isophthalamic acid pentafluorophenyl ester (0.08g, 45.2%). To a suspension of 4,5-difluoro-6-(-4-iodo-2-methyl-phenylamino)-N-methyl-isophthalamic acid pentafluorophenyl ester (0.08 g, 0.13 mmol) in freshly distilled THF (3 mL) is added cyclopropylmethylamine hydrochloride (0.016 g, 0.13 mmol), and N,N-diisopropylethylamine (0.07 mL, 0.39 mmol). After stirring at room temperature for 17 hours the reaction mixture was partitioned between ethyl acetate and 1.0 M HCl solution. The organic layer was washed twice with water, twice with saturated brine solution, dried over MgSO4, filtered and concentrated in vacuo. Purification was performed by silica column chromatography in 2:1 ethyl acetate:hexanes affording N1-cyclopropylmethoxy-4,5-difluoro-6-(4-iodo-2-methyl-phenylamino)-N3-methyl-isophthalamide (0.033, 42.8%); mp 198–202° C.; 1H NMR (400 MHz; DMSO-d6) 8.59 (s, 1H), 8.01 (s, 1H), 7.44 (d, 1H, J=5.2), 7.32 (s, 1H), 7.18 (d, 1H, J=7.6), 6.36 (m,1H), 3.34 (d, 2H, J=6.8), 2.56 (d, 3H, J=4.0), 1.99 (s, 3H), 0.82 (m, 1H), 0.27 (d, 2H, J=8.4), 0.00 (m, 2H); MS(APCI)m+1=516;

Workup

  1. customtransferred to a separatory funnel
  2. washwashed twice with 1.0 M HCl, twice with 5% aqueous NaHCO3 solution, 2 times with water and once with saturated brine solution
  3. customThe organic layers were collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e5c785ec54c544ef86fd7bc0247f9e2b
Source dataset
uspto-grants-2006_02
Patent number
US07001905B2

Reaction notes

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