Ethylamine → N,N'-diethyl-2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]pentanediamide

HRID 1402587Notes

Reaction equation

HRID 1402587 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:29]([C:32]([NH:34][C:35]2[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:36]=2[F:42])=[O:33])=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C:11]2[NH:15][CH:14]=[C:13]([C:16]([NH:18][CH:19]([CH2:23][CH2:24][C:25]([OH:27])=O)[C:20](O)=[O:21])=[O:17])[CH:12]=2)[CH:6]=1.Cl.C[N:45](C)[CH2:46][CH2:47]CN=C=NCC.[CH2:55]([NH2:57])[CH3:56].C1COCC1>CN(C=O)C.O>[CH2:55]([NH:57][C:20](=[O:21])[CH:19]([NH:18][C:16]([C:13]1[CH:12]=[C:11]([C:7]2[CH:6]=[C:5]([O:4][C:3]3[CH:28]=[C:29]([C:32]([NH:34][C:35]4[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:36]=4[F:42])=[O:33])[CH:30]=[CH:31][C:2]=3[F:1])[CH:10]=[CH:9][N:8]=2)[NH:15][CH:14]=1)=[O:17])[CH2:23][CH2:24][C:25]([NH:45][CH2:46][CH3:47])=[O:27])[CH3:56]

Participants

7

Reactant 4

HCID 6341EthylamineHCID 8028TetrahydrofuranHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712935772-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]pentanedioic acid

Product 1

HCID 71293595N,N'-diethyl-2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]pentanediamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]pentanedioic acid (100 mg, 0.17 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC, 83 mg, 0.43 mmol) in 10 ml of anhydrous DMF was added 2M ethylamine solution in THF (0.43 ml, 0.86 mmol). The mixture was stirred at room temperature for overnight and poured into 100 ml of water. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 5-8% of methanol in chloroform to afford N,N′-diethyl-2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]pentanediamide as white solid. Yield: 76 mg, 69%.

Workup

  1. filtrationThe precipitates were filtered
  2. washwashed with water
  3. customdried in vacuo
  4. customto give the crude, which
  5. customwas purified by silica gel chromatography
  6. washeluting with 5-8% of methanol in chloroform

Sources & evidence

ORD record
ord-8012355d0b9c43d3874614198388f016
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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