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

HRID 525806Notes

Reaction equation

HRID 525806 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([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: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][N:1]([CH2:45][C:44]([O:57][CH3:56])=[O:52])[CH2:47][C:48]([O:50][CH3:51])=[O:49])=[O:7])[S:16][C:15]=12

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 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 86290666Dimethyl 2,2'-({3-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propyl}imino)diacetate

Conditions

Temperature
60 °C

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 (77 mg, 0.60 mmol) in 10 ml of anhydrous DMF was added methyl bromoacetate (92 mg, 0.60 mmol). The mixture was heated at 60° C. for 1 hour 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 3˜4% of MeOH in CHCl3 to afford dimethyl 2,2′-({3-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propyl}imino)diacetate as white solid. Yield: 140 mg, 88%.

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 3˜4% of MeOH in CHCl3

Sources & evidence

ORD record
ord-f64ea1f5f2d74685a1900c68690d6831
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

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