1,1,3,3-Tetramethylguanidine → HCID 178499694, compound

HRID 1058420Notes

Reaction equation

HRID 1058420 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].CC(C)(OC([N:47]1[C:51]2[CH:52]=[CH:53][C:54]([CH:56]=O)=[CH:55][C:50]=2[N:49]=[N:48]1)=O)C>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:56]/[C:54]1[CH:53]=[CH:52][C:51]2[NH:47][N:48]=[N:49][C:50]=2[CH:55]=1

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 11637374tert-Butyl 5-formyl-1H-benzo[d][1,2,3]triazole-1-carboxylateHCID 23560709Rac.-n-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 178499694HCID 178499694, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,1,3,3-Tetramethylguanidine (0.5 mL, 3.97 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, 1.89 mmol) in tetraliydrofuran (3 mL) at −20° C. After 10 min, a solution of 1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazole-5-carboxaldehyde (Example 40; 467 mg, 1.89 mmol) in tetrahydrofuran (3 mL) was added. The solution was stirred at room temperature for 1 h, then the solvent was evaporated and the residue was dissolved in a mixture of trifluoroacetic acid/dichloromethane (1:1; 4 mL). After the solution was stirred at room temperature for 2 h, the solvent was evaporated and the residue co-evaporated with toluene (2×5 mL) to remove residual trifluoroacetic acid. Ethyl acetate (20 mL) was added and the solution was washed with 5% sodium bicarbonate solution (20 mL). After the aqueous layer was back extracted with ethyl acetate, the combined organic layers were dried (MgSO4), filtered and evaporated to dryness. The residual material was chromatographed over silica gel (5-10% methanol/dichloromethane) to give (Z)-3-(1H-benzotriazol-5-yl)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]propenoic acid methyl ester (690 mg, 66% yield) as a colorless solid.

Workup

  1. customthe solvent was evaporated
  2. dissolutionthe residue was dissolved in a mixture of trifluoroacetic acid/dichloromethane (1:1; 4 mL)
  3. stirringAfter the solution was stirred at room temperature for 2 h
  4. customthe solvent was evaporated
  5. customthe residue co-evaporated with toluene (2×5 mL) to remove residual trifluoroacetic acid
  6. additionEthyl acetate (20 mL) was added
  7. washthe solution was washed with 5% sodium bicarbonate solution (20 mL)
  8. extractionAfter the aqueous layer was back extracted with ethyl acetate
  9. dry with materialthe combined organic layers were dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated to dryness
  12. customThe residual material was chromatographed over silica gel (5-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-66b32d6544bd4099b373151a324df2db
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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