Tetrahydrofuran → HCID 23598853, compound

HRID 890940Notes

Reaction equation

HRID 890940 reaction equation
FC1C(O[C:9](=[O:31])[C:10]2[C:19]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=3[CH3:28])=[C:18]([F:29])[C:17]([F:30])=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[CH:11]=2)=C(F)C(F)=C(F)C=1F.Cl.C1(C[NH2:41])CC1.C(N(CC)C(C)C)(C)C.[CH2:51]1[CH2:55][O:54][CH2:53][CH2:52]1>>[CH:51]1([CH2:55][O:54][NH:41][C:9](=[O:31])[C:10]2[C:19]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=3[CH3:28])=[C:18]([F:29])[C:17]([F:30])=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[CH:11]=2)[CH2:52][CH2:53]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 81671(Cyclopropylmethyl)ammonium chlorideHCID 86590369HCID 86590369, compound

Product 1

HCID 23598853HCID 23598853, compoundYield 42.8%

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. customwas partitioned between ethyl acetate and 1.0 M HCl solution
  2. washThe organic layer was washed twice with water, twice with saturated brine solution
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification

Sources & evidence

ORD record
ord-27144d82b53c46318fc81437a9b5a208
Source dataset
uspto-grants-2006_02
Patent number
US07001905B2

Reaction notes

Loading…