Water → methyl ({3-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propyl}amino)acetate

HRID 1402548Notes

Reaction equation

HRID 1402548 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([O:19][C:20]3[CH:25]=[C:24]([C:26]([NH:28][C:29]4[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=4[F:36])=[O:27])[CH:23]=[CH:22][C:21]=3[F:37])[CH:16]=[CH:15][N:14]=2)[NH:10][CH:9]=1)=[O:7].C(N(CC)C(C)C)(C)C.Br[CH2:48][C:49]([O:51][CH3:52])=[O:50].O>CN(C=O)C>[F:37][C:21]1[CH:22]=[CH:23][C:24]([C:26]([NH:28][C:29]2[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=2[F:36])=[O:27])=[CH:25][C:20]=1[O:19][C:17]1[CH:16]=[CH:15][N:14]=[C:13]([C:11]2[NH:10][CH:9]=[C:8]([C:6]([NH:5][CH2:4][CH2:3][CH2:2][NH:1][CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:7])[CH:12]=2)[CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 71293544N-(3-aminopropyl)-5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxamide

Product 1

HCID 71541782methyl ({3-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propyl}amino)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-(3-aminopropyl)-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 (52 mg, 0.40 mmol) in 10 ml of anhydrous DMF was added methyl bromoacetate (30 mg, 0.20 mmol). The mixture was stirred at room temperature for 50 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 methyl ({3-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propyl}amino)acetate as white solid. Yield: 40 mg, 35%.

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-551edeaa6ff34b9892457a14fd88e39e
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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