1,2-Dichloroethane → Tert-butyl (5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}benzyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidine-1-carboxylate

HRID 243733Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243733
[NH2:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][C@H:9]([C@H:12]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:8]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:4][CH:3]=1.[NH2:36][C:37]1[S:38][CH:39]=[C:40]([CH2:42][C:43](O)=[O:44])[N:41]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:36][C:37]1[S:38][CH:39]=[C:40]([CH2:42][C:43]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:6][CH:7]3[CH2:11][CH2:10][C@H:9]([C@H:12]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[N:8]3[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:34][CH:35]=2)=[O:44])[N:41]=1

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 34665(2-Amino-1,3-thiazol-4-yl)acetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 57907571Tert-butyl(5R)-2-(4-aminobenzyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidine-1-carboxylate

Produkt 1

HCID 57907587Tert-butyl (5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}benzyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidine-1-carboxylateAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of 10 mg (5:1 mixture cis/trans, 0.02 mmol) of tert-butyl(5R)-2-(4-aminobenzyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pyrrolidine-1-carboxylate (i-3) and (2-amino-1,3-thiazol-4-yl)acetic acid (3.18 mg, 0.02 mmol) in 0.5 mL anhydrous DMF was added a 0.5 M solution of HOAt in DMF (0.04 mL, 0.02 mmol) followed by EDC (5.8 mg, 0.03 mmol) and DIEA (3.5 μL, 0.02 mmol). The resulting mixture was stirred at room temperature under nitrogen atmosphere for 16 h. The mixture was washed with water and extracted with dichloromethane (2×2 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by preparative TLC plate (500 uM) eluting with 5% MeOH in dichloromethane to afforded the product (10.3 mg, 81%). m/z (ES) 637 (MH)+, 659 (MNa)+.

Aufarbeitung

  1. washThe mixture was washed with water
  2. extractionextracted with dichloromethane (2×2 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by preparative TLC plate (500 uM)
  7. washeluting with 5% MeOH in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-fc0f8ec95a2148b692246adb2ad2da31
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653260B2

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