Water → Methyl ({3-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propyl}amino)acetate

HRID 525805Notes

Reaction equation

HRID 525805 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[S:16][C:15]2[C:10](=[N:11][CH:12]=[CH:13][C:14]=2[O:17][C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][C:28]3[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:29]=3[F:35])=[O:26])=[C:20]([F:36])[CH:19]=2)[CH:9]=1)=[O:7].C(N(CC)C(C)C)(C)C.Br[CH2:47][C:48]([O:50][CH3:51])=[O:49].O>CN(C=O)C>[F:36][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[NH:24][C:25]([NH:27][C:28]1[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:29]=1[F:35])=[O:26])[O:17][C:14]1[CH:13]=[CH:12][N:11]=[C:10]2[CH:9]=[C:8]([C:6]([NH:5][CH2:4][CH2:3][CH2:2][NH:1][CH2:47][C:48]([O:50][CH3:51])=[O:49])=[O:7])[S:16][C:15]=12

Participants

6

Reactant 4

HCID 962WaterHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 86290844N-(3-aminopropyl)-7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxamide

Product 1

HCID 86290665Methyl ({3-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propyl}amino)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-(3-aminopropyl)-7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxamide (125 mg, 0.24 mmol) and N,N-diisopropylethylamine (46 mg, 0.36 mmol) in 10 ml of anhydrous DMF was added methyl bromoacetate (36 mg, 0.24 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 5˜8% of MeOH in CHCl3 to afford methyl ({3-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propyl}amino)acetate as light beige solid. Yield: 54 mg, 38%.

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 5˜8% of MeOH in CHCl3

Sources & evidence

ORD record
ord-3c612a27325f4a9da3d21e7e84362558
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

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