1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester

HRID 1058421Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1058421
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:41])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33].[CH3:42][C:43]([CH3:59])([O:45][C:46]([N:48]1[C:52]2[CH:53]=[CH:54][C:55]([CH:57]=O)=[CH:56][C:51]=2[N:50]=[N:49]1)=[O:47])[CH3:44]>O1CCCC1>[CH3:9][O:10][C:11](=[O:41])/[C:12](/[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33])=[CH:57]/[C:55]1[CH:54]=[CH:53][C:52]2[N:48]([C:46]([O:45][C:43]([CH3:42])([CH3:59])[CH3:44])=[O:47])[N:49]=[N:50][C:51]=2[CH:56]=1

Komponenten

5

Edukt 3

HCID 664601,1,3,3-TetramethylguanidineHCID 11637374tert-Butyl 5-formyl-1H-benzo[d][1,2,3]triazole-1-carboxylateHCID 23560749Rac.-n-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Produkt 1

HCID 70027820(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl esterAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

1,1,3,3-Tetramethylguanidine (60 μL, 0.48 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 132; 109 mg, 0.22 mmol) in tetrahydrofuran (3 mL) at room temperature. 1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazole-5-carboxaldehyde (Example 40; 55 mg, 0.22 mmol) was added and the solution was stirred at room temperature for 42 h. After the solvents were removed under reduced pressure, the residue was partitioned between ethyl acetate (10 mL) and pH 6 phosphate buffer (5 mL). The organic phase was washed with pH 6 phosphate buffer, brine, 10% aqueous sodium bicarbonate solution and brine. Each of the aqueous layers was extracted in turn with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and evaporated to give crude (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester (120 mg) which was used directly in the next step.

Aufarbeitung

  1. customAfter the solvents were removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate (10 mL) and pH 6 phosphate buffer (5 mL)
  3. washThe organic phase was washed with pH 6 phosphate buffer, brine, 10% aqueous sodium bicarbonate solution and brine
  4. extractionEach of the aqueous layers was extracted in turn with ethyl acetate
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-fe192756bfc84784af3927818578d554
Quelldatensatz
uspto-grants-2003_02
Patentnummer
US06515124B2

Notizen zur Reaktion

Wird geladen…