Water → HCID 71293538, compound

HRID 1402564Notes

Reaction equation

HRID 1402564 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]=[CH:23][C:22]([NH:25][C:26]([NH:28][C:29]4[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=4[F:36])=[O:27])=[C:21]([F:37])[CH:20]=3)[CH:15]=[CH:14][N:13]=2)[NH:9][CH:8]=1)=[O:6].C(N(CC)C(C)C)(C)C.Br[CH2:48][C:49]([O:51][CH3:52])=[O:50].[OH2:53].C1[CH2:58][O:57][CH2:56][CH2:55]1>>[F:37][C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][C:22]=1[NH:25][C:26]([NH:28][C:29]1[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=1[F:36])=[O:27])[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]([CH2:55][C:56]([O:57][CH3:58])=[O:53])[CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:6])[CH:11]=2)[CH:17]=1

Participants

6

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 71293568HCID 71293568, compound

Product 1

HCID 71293538HCID 71293538, compound

Conditions

Temperature
55 °C

Procedure

To a stirred suspension of N-(2-aminoethyl)-5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxamide (120 mg, 0.24 mmol) in 10 ml of anhydrous THF were added N,N-diisopropylethylamine (1 ml, 5.6 mmol) and methyl bromoacetate (300 mg, 2.0 mmol). The mixture was heated at 55° C. for 2 hours 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′-[(2-{[(5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}ethyl)imino]diacetate as white solid. Yield: 110 mg, 71%.

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-9cae68bfd5014f228a4ecf49fe963105
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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