Water → HCID 71293523, compound

HRID 1402546Notes

Reaction equation

HRID 1402546 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([CH2:45][CH3:46])C(C)C)(C)C.Br[CH2:48][C:49]([O:51][CH3:52])=[O:50].[OH2:53].CN([CH:57]=[O:58])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][N:1]([CH2:46][C:45]([O:58][CH3:57])=[O:53])[CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:7])[CH:12]=2)[CH:18]=1

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 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 71293523HCID 71293523, compound

Conditions

Temperature
55 °C

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 (85 mg, 0.17 mmol) and N,N-diisopropylethylamine (100 mg, 0.78 mmol) in 10 ml of anhydrous DMF was added methyl bromoacetate (100 mg, 0.65 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 3˜5% of MeOH in CHCl3 to afford dimethyl 2,2′-({3-[([5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl]carbonyl)amino]propyl}imino)diacetate as white solid. Yield: 70 mg, 64%.

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˜5% of MeOH in CHCl3

Sources & evidence

ORD record
ord-a8f7b6d5cc23472cadcafcb4b564aaa1
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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