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

HRID 1402600Notes

Reaction equation

HRID 1402600 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:20]([C:23]([NH:25][C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=2[F:33])=[O:24])=[CH:19][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](O)=[O:17])[CH:12]=2)[CH:6]=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.[NH2:67][C@H:68]([C:75]([O-:77])=[O:76])[CH2:69][CH2:70][C:71]([O:73][CH3:74])=[O:72].Cl>CN(C=O)C.O>[F:1][C:2]1[CH:22]=[CH:21][C:20]([C:23]([NH:25][C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=2[F:33])=[O:24])=[CH:19][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:67][CH:68]([CH2:69][CH2:70][C:71]([O:73][CH3:74])=[O:72])[C:75]([OH:77])=[O:76])=[O:17])[CH:12]=2)[CH:6]=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 21115276L-glutamate gamma-methyl esterHCID 510015405-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylic acid

Product 1

HCID 712935982-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-methoxy-5-oxopentanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylic acid (60 mg, 0.13 mmol) in 10 ml of anhydrous DMF were added HATU (61 mg, 0.16 mmol) and N,N-diisopropylethylamine (52 mg, 0.40 mmol). The mixture was stirred at room temperature for 10 minutes, followed by addition of 5-methyl L-glutamate (32 mg, 0.20 mmol). The mixture was heated at 60° C. for 1 hour, cooled to room temperature and poured into 100 ml of water with vigorous stirring. 2M HCl was added slowly until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give 2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-methoxy-5-oxopentanoic acid as white solid. Yield: 30 mg, 38%.

Workup

  1. temperatureThe mixture was heated at 60° C. for 1 hour
  2. temperaturecooled to room temperature
  3. filtrationThe precipitates were filtered
  4. washwashed with water
  5. customdried in vacuo

Sources & evidence

ORD record
ord-ea8e7c3cf5c040a9aeac9a57c19ddc10
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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