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

HRID 1402613Notes

Reaction equation

HRID 1402613 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][C:25]([C:28]([NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=2)=[O:29])=[CH:24][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][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[O:17])[CH:12]=2)[CH:6]=1.[CH3:38]N(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.COC(=O)CCN.Cl>CN(C=O)C.O>[F:1][C:2]1[CH:27]=[CH:26][C:25]([C:28]([NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=2)=[O:29])=[CH:24][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][CH2:19][CH2:20][C:21]([O:23][CH3:38])=[O:22])=[O:17])[CH:12]=2)[CH:6]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712936193-[({5-[4-(2-fluoro-5-{[(3-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propanoic acid

Product 1

HCID 71293559methyl 3-[({5-[4-(2-fluoro-5-{[(3-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-[4-(2-fluoro-5-{[(3-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylic acid (Example 275) (100 mg, 0.23 mmol) in 10 ml of anhydrous DMF were added HATU (100 mg, 0.26 mmol) and N,N-diisopropylethylamine (85 mg, 0.66 mmol). The mixture was stirred at room temperature for 10 minutes, followed by addition of β-alanine methyl ester hydrochloride (46 mg, 0.33 mmol). The mixture was stirred for another minutes and poured into 100 ml of water. 2M HCl was added dropwise with vigorous stirring until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give methyl 3-[({5-[4-(2-fluoro-5-{[(3-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propanoate as white solid. Yield: 110 mg, 92%.

Workup

  1. stirringThe mixture was stirred for another minutes
  2. stirringwith vigorous stirring until pH=4
  3. filtrationThe precipitates were filtered
  4. washwashed with water
  5. customdried in vacuo

Sources & evidence

ORD record
ord-ca8603d8391d4cd7b093285f9efacd6a
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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