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

HRID 1058434Notes

Reaction equation

HRID 1058434 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[N:45]=[CH:46][S:47][C:48]=1[CH:49]=O)[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:49]/[C:48]1[S:47][CH:46]=[N:45][C:44]=1[CH:42]([CH3:43])[CH3:41]

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 110841114-Isopropylthiazole-5-carbaldehydeHCID 23560750HCID 23560750, compound

Product 1

HCID 59038382(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[4-(1-methylethyl)thiazol-5-yl]propenoic acid methyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,1,3,3-Tetramethylguanidine (41 μL, 0.33 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 141; 75 mg, 0.15 mmol) in tetrahydrofuran (2 mL) at about −25° C. After 5 min, a solution of 4-(1-methylethyl)thiazole-5-carboxaldehyde (Example 56; 26 mg, 0.168 mmol) in tetrahydrofuran (1 mL) was added. The cooling bath was removed and the solution was stirred at room temperature for 17 h. The solvent was evaporated and the residue was partitioned between ethyl acetate (10 mL) and 10% aqueous acetic acid (5 mL). The ethyl acetate layer was washed with brine and each of the aqueous layers was extracted with ethyl acetate (10 mL). The combined organic extracts were dried (Na2SO4), filtered and evaporated to give a colorless foam which was triturated with diethyl ether (5 mL). The resulting solids were recovered by filtration to furnish (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[4-(1-methylethyl)thiazol-5-yl]propenoic acid methyl ester (76 mg, 99% yield).

Workup

  1. customThe cooling bath was removed
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between ethyl acetate (10 mL) and 10% aqueous acetic acid (5 mL)
  4. washThe ethyl acetate layer was washed with brine
  5. extractioneach of the aqueous layers was extracted with ethyl acetate (10 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give a colorless foam which
  10. customwas triturated with diethyl ether (5 mL)
  11. filtrationThe resulting solids were recovered by filtration

Sources & evidence

ORD record
ord-81df4a099da74bd58ba85c4214871a01
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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