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

HRID 1058417Notes

Reaction equation

HRID 1058417 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].[CH3:41][C:42]1[S:43][CH:44]=[C:45]([CH:47]=O)[N:46]=1>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[Br:32])=[CH:47]/[C:45]1[N:46]=[C:42]([CH3:41])[S:43][CH:44]=1

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 27631912-Methyl-1,3-thiazole-4-carbaldehydeHCID 23560709Rac.-n-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59038453(Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-methylthiazol-4-yl)propenoic acid methyl esterYield 91.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

1,1,3,3-Tetramethylguanidine (50 μL, 0.397 mmol) was added to a solution of rac.-N-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 130; 100 mg, 0.189 mmol) in tetrahydrofuran (2 mL) at −40° C. The solution was stirred at −40° C. for 5 min and then 2-methylthiazole-4-carboxaldehyde (Example 41; 48 mg, 0.378 mmol) was added. The solution was stirred at −40° C. for 1 h and then allowed to stir at room temperature for 4 h. The solution was quenched with pH 6 phosphate buffer, diluted with ethyl acetate (15 mL) and the separated organic layer was washed with pH 6 phosphate buffer (10 mL) and brine (10 mL). The organic phase was dried (MgSO4), filtered, evaporated and triturated with diethyl ether to give (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-methylthiazol-4-yl)propenoic acid methyl ester (92 mg, 49% yield) as a brown solid.

Workup

  1. stirringThe solution was stirred at −40° C. for 1 h
  2. stirringto stir at room temperature for 4 h
  3. customThe solution was quenched with pH 6 phosphate buffer
  4. additiondiluted with ethyl acetate (15 mL)
  5. washthe separated organic layer was washed with pH 6 phosphate buffer (10 mL) and brine (10 mL)
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-cf37afb81d61438ca8df18beb47504b5
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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