1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-ethyl-4-methylthiazole-5-yl)propenoic acid methyl ester

HRID 1058425Notes

Reaction equation

HRID 1058425 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[Cl:32].[CH2:41]([C:43]1[S:44][C:45]([CH:49]=O)=[C:46]([CH3:48])[N:47]=1)[CH3:42]>ClCCl>[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[Cl:32])=[CH:49]/[C:45]1[S:44][C:43]([CH2:41][CH3:42])=[N:47][C:46]=1[CH3:48]

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 186730525-Thiazolecarboxaldehyde, 2-ethyl-4-methyl-HCID 23560750HCID 23560750, compound

Product 1

HCID 59038457(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-ethyl-4-methylthiazole-5-yl)propenoic acid methyl esterYield 35.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

1,1,3,3-Tetramethylguanidine (107 mg, 0.9 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 141; 300 mg, 0.6 mmol) in dichloromethane (10 mL) at ˜5° C. The solution was stirred at ˜5° C. for 30 min and then 2-ethyl-4-methylthiazole-5-carboxaldehyde (Example 60; 192 mg, 1.2 mmol) was added. The solution was stirred overnight at room temperature, then silica gel was added and the solvent was evaporated. The residue was applied to a column of silica gel and unreacted 2-ethyl-4-methylthiazole-5-carboxaldehyde was eluted with 50% ethyl acetate/hexanes. Evaporation of the appropriate fractions eluted with 5% methanol/dichloromethane gave (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-ethyl-4-methylthiazole-5-yl)propenoic acid methyl ester (110 mg, 35% yield) as a colorless solid, mp>200° C.

Workup

  1. stirringThe solution was stirred overnight at room temperature
  2. additionsilica gel was added
  3. customthe solvent was evaporated
  4. washwas eluted with 50% ethyl acetate/hexanes
  5. customEvaporation of the appropriate fractions
  6. washeluted with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-a83329119b044d29b26eda72da1135f5
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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