Hydrochloric Acid → HCID 71293525, compound

HRID 1402607Notes

Reaction equation

HRID 1402607 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=1[F:34])=[O:25])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17](O)=[O:18])[CH:13]=2)[CH:7]=1.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.[CH3:69][O:70][C:71](=[O:80])[C@H:72]([CH2:74][CH2:75][C:76]([O:78][CH3:79])=[O:77])[NH2:73].Cl>CN(C=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=1[F:34])=[O:25])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17]([NH:73][CH:72]([CH2:74][CH2:75][C:76]([O:78][CH3:79])=[O:77])[C:71]([O:70][CH3:69])=[O:80])=[O:18])[CH:13]=2)[CH:7]=1

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 12917568Dimethyl L-glutamate hydrochlorideHCID 51001123HCID 51001123, compound

Product 1

HCID 71293525HCID 71293525, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid (120 mg, 0.26 mmol), HATU (110 mg, 0.29 mmol) and N,N-diisopropylethylamine (100 mg, 0.78 mmol) in anhydrous DMF (10 ml) was stirred at room temperature for 10 minutes, followed by addition of L-glutamic acid dimethyl ester hydrochloride (66 mg, 0.31 mmol). The mixture was heated at 50° C. for 15 minutes, cooled to room temperature and poured into 100 ml of water with vigorous stirring. 2M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give dimethyl 2-{[(5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}pentanedioate as white solid. Yield: 130 mg, 81%.

Workup

  1. temperatureThe mixture was heated at 50° C. for 15 minutes
  2. temperaturecooled to room temperature
  3. filtrationThe precipitates were filtered
  4. washwashed with water
  5. customdried in vacuo

Sources & evidence

ORD record
ord-8deb33ed3ece4630ba896bba03addb0f
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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