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

HRID 1058435Notes

Reaction equation

HRID 1058435 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].[CH3:41][CH:42]([C:44]1[S:45][C:46]([CH:50]=O)=[C:47]([CH3:49])[N:48]=1)[CH3:43]>O1CCCC1>[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:50]/[C:46]1[S:45][C:44]([CH:42]([CH3:41])[CH3:43])=[N:48][C:47]=1[CH3:49]

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 186730515-Thiazolecarboxaldehyde, 4-methyl-2-(1-methylethyl)-HCID 23560750HCID 23560750, compound

Product 1

HCID 59038367(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl]propenoic acid methyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,1,3,3-Tetramethylguanidine (55 μL, 0.44 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 141; 100 mg, 0.20 mmol) in tetrahydrofuran (4 mL) at about −20° C. After 5 min, a solution of 2-(1-methylethyl)-4-methylthiazole-5-carboxaldehyde (Example 57; 38 mg, 0.225 mmol) in tetrahydrofuran (1 mL) was added. After 2 min, the cooling bath was removed and the solution was stirred at room temperature for 66 h. The solvent was evaporated and ethyl acetate (10 mL) and 10% aqueous acetic acid (5 mL) were added to the residue. The mixture was filtered to give (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl]propenoic acid methyl ester (65 mg, 62% yield) as a colorless solid.

Workup

  1. waitAfter 2 min
  2. customthe cooling bath was removed
  3. customThe solvent was evaporated
  4. additionethyl acetate (10 mL) and 10% aqueous acetic acid (5 mL) were added to the residue
  5. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-b9d9c7ae75024b8094ccb9374654c425
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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