Hydrochloric Acid → ethyl 5-{[(5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}pentanoate

HRID 1402538Notes

Reaction equation

HRID 1402538 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:33]=[CH:32][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29](O)=[O:30])[CH:25]=3)[CH:19]=2)=[CH:15][CH:14]=1)=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[NH2:68][CH2:69][CH2:70][CH2:71][CH2:72][C:73]([O:75][CH2:76][CH3:77])=[O:74].Cl>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:33]=[CH:32][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29]([NH:68][CH2:69][CH2:70][CH2:71][CH2:72][C:73]([O:75][CH2:76][CH3:77])=[O:74])=[O:30])[CH:25]=3)[CH:19]=2)=[CH:15][CH:14]=1)=[O:11]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16094861Ethyl 5-aminopentanoate hydrochlorideHCID 510012875-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid

Product 1

HCID 71293555ethyl 5-{[(5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}pentanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid (300 mg, 0.67 mmol), HATU (281 mg, 0.74 mmol) and N,N-diisopropylethylamine (258 mg, 2.0 mmol) in anhydrous DMF (10 ml) was stirred at room temperature for 10 minutes, followed by addition of ethyl 5-aminovalerate hydrochloride (145 mg, 0.80 mmol). The mixture was stirred for another 10 minutes and poured into 100 ml of water. 2M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 3˜5% of methanol in chloroform to give ethyl 5-{[(5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}pentanoate as white solid. Yield: 288 mg, 75%.

Workup

  1. stirringThe mixture was stirred for another 10 minutes
  2. filtrationThe precipitates were filtered
  3. washwashed with water
  4. customdried in vacuo
  5. customto give the crude, which
  6. customwas purified by silica gel chromatography
  7. washeluting with 3˜5% of methanol in chloroform

Sources & evidence

ORD record
ord-11d55cdcaab34f72bee8266cb0862e6f
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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