Water → dimethyl 2,2'-({2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]ethyl}imino)diacetate

HRID 1402547Notes

Reaction equation

HRID 1402547 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[C:16]([O:18][C:19]3[CH:24]=[C:23]([C:25]([NH:27][C:28]4[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:29]=4[F:35])=[O:26])[CH:22]=[CH:21][C:20]=3[F:36])[CH:15]=[CH:14][N:13]=2)[NH:9][CH:8]=1)=[O:6].C(N([CH2:44][CH3:45])C(C)C)(C)C.Br[CH2:47][C:48]([O:50][CH3:51])=[O:49].[OH2:52].CN([CH:56]=[O:57])C>>[F:36][C:20]1[CH:21]=[CH:22][C:23]([C:25]([NH:27][C:28]2[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:29]=2[F:35])=[O:26])=[CH:24][C:19]=1[O:18][C:16]1[CH:15]=[CH:14][N:13]=[C:12]([C:10]2[NH:9][CH:8]=[C:7]([C:5]([NH:4][CH2:3][CH2:2][N:1]([CH2:45][C:44]([O:57][CH3:56])=[O:52])[CH2:47][C:48]([O:50][CH3:51])=[O:49])=[O:6])[CH:11]=2)[CH:17]=1

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 71293631N-(2-aminoethyl)-5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxamide

Product 1

HCID 71293510dimethyl 2,2'-({2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]ethyl}imino)diacetate

Conditions

Temperature
55 °C

Procedure

To a stirred solution of N-(2-aminoethyl)-5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxamide (100 mg, 0.20 mmol) and N,N-diisopropylethylamine (129 mg, 1.0 mmol) in 10 ml of anhydrous DMF was added methyl bromoacetate (77 mg, 0.50 mmol). The mixture was heated at 55° C. for 30 minutes and poured into 100 ml of water with vigorous stirring. The precipitates were filtered and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 2-3% of MeOH in CHCl3 to afford dimethyl 2,2′-({2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]ethyl}imino)diacetate as off-white solid. Yield: 80 mg, 62%.

Workup

  1. filtrationThe precipitates were filtered
  2. customdried in vacuo
  3. customto give the crude, which
  4. customwas purified by silica gel chromatography
  5. washeluting with 2-3% of MeOH in CHCl3

Sources & evidence

ORD record
ord-66d0f3ca36f14e9ca0b44c25e4618d0c
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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