Hydrochloric Acid → Methyl 3-[({7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propanoate

HRID 525797Notes

Reaction equation

HRID 525797 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:31]=[CH:30][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[CH:24]=[C:25]([C:27]([OH:29])=O)[S:26][C:19]=23)=[CH:15][CH:14]=1)=[O:11].CN([C:35]([O:39]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:59]([CH2:63][CH3:64])C(C)C)(C)C.N1CC[C@@H:67]([OH:70])C1.Cl>C1COCC1.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:31]=[CH:30][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[CH:24]=[C:25]([C:27]([NH:59][CH2:63][CH2:64][C:67]([O:39][CH3:35])=[O:70])=[O:29])[S:26][C:19]=23)=[CH:15][CH:14]=1)=[O:11]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 509151257-[4-({[(2-Fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxylic acid

Product 1

HCID 51041815Methyl 3-[({7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxylic acid (120 mg, 0.27 mmol), HATU (122 mg, 0.32 mmol) and N,N-diisopropylethylamine (105 mg, 0.81 mmol) in anhydrous THF (10 ml) was stirred at room temperature for 10 minutes, followed by addition of (R)-3-pyrrolidinol (56 mg, 0.40 mmol). The mixture was heated and stirred at 60° C. for 30 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 methyl 3-[({7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]propanoate as white solid. Yield: 128 mg, 90%.

Workup

  1. temperatureThe mixture was heated
  2. stirringstirred at 60° C. for 30 minutes
  3. filtrationThe precipitates were filtered
  4. washwashed with water
  5. customdried in vacuo

Sources & evidence

ORD record
ord-236a82917c5b42f68a9ebacd04602c75
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

Loading…