Phosphate → (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester

HRID 1058415Notes

Reaction equation

HRID 1058415 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:40])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:33])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:22])=[CH:17][C:16]=1[Br:32].[N:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:44]=[C:43]([CH:51]=O)[CH:42]=1.P([O-])([O-])([O-])=O>O1CCCC1.C(OCC)(=O)C>[CH3:9][O:10][C:11](=[O:40])/[C:12](/[NH:13][C:14](=[O:33])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:22])=[CH:17][C:16]=1[Br:32])=[CH:51]/[C:43]1[CH:42]=[N:41][C:50]2[C:45]([CH:44]=1)=[CH:46][CH:47]=[CH:48][CH:49]=2

Participants

7

Reactant 4

HCID 1061PhosphateHCID 664601,1,3,3-TetramethylguanidineHCID 836413-QuinolinecarboxaldehydeHCID 23560709Rac.-n-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59038399(Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl esterYield 47%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-45 °C

Procedure

1,1,3,3-Tetramethylguanidine (0.5 mL, 4.0 mmol) was added to a solution of rac.-N-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 130; 1.00 g, 1.9 mmol) in tetrahydrofuran (8 mL) at −45° C. The solution was stirred at −45° C. for 5 min and then quinoline-3-carboxaldehyde (300 mg, 1.9 mmol) was added. After the reaction was allowed to proceed at −40° C. for 30 min, the mixture was warmed to room temperature and was stirred for another 2 h. Ethyl acetate and pH 6 phosphate buffer (200 mL each) were added and the resulting solid was filtered to furnish (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (500 mg, 47% yield). The layers in the filtrate were separated and the aqueous phase was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried (MgSO4), filtered through a bed of silica gel and the filtrate was evaporated to give an additional quantity of (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (520 mg, 49% yield) as a colorless solid.

Workup

  1. waitto proceed at −40° C. for 30 min
  2. temperaturethe mixture was warmed to room temperature
  3. stirringwas stirred for another 2 h
  4. filtrationthe resulting solid was filtered

Sources & evidence

ORD record
ord-adfd9aed60ef4641beb5157e2db64b19
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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