(2-Amino-1,3-thiazol-4-yl)acetic acid → Tert-butyl (2S,5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate

HRID 243741Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243741
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][C@@H:7]2[CH2:11][CH2:10][C@H:9]([C@H:12]([OH:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:8]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:4][C:3]=1[Br:29].[NH2:30][C:31]1[S:32][CH:33]=[C:34]([CH2:36][C:37](O)=[O:38])[N:35]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)CCl>[NH2:30][C:31]1[S:32][CH:33]=[C:34]([CH2:36][C:37]([NH:1][C:2]2[CH:28]=[CH:27][C:5]([CH2:6][C@@H:7]3[CH2:11][CH2:10][C@H:9]([C@H:12]([OH:19])[C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[N:8]3[C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])=[CH:4][C:3]=2[Br:29])=[O:38])[N:35]=1

Komponenten

7

Edukt 4

HCID 34665(2-Amino-1,3-thiazol-4-yl)acetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57907390Tert-butyl(2S,5R)-2-(4-amino-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate

Produkt 1

HCID 57907380Tert-butyl (2S,5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylateAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 115 mg (0.25 mmol) of tert-butyl (2S,5R)-2-(4-amino-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate (i-80a) and (2-amino-1,3-thiazol-4-yl)acetic acid (77 mg, 0.30 mmol) in 3.0 mL anhydrous DMF was added HOBt (44 mg, 0.32 mmol) followed by EDC (66 mg) and DIEA (0.22 mL, 1.25 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 Gilson reverse phase HPLC eluting with a gradient of 10-90% acetonitrile in water with 0.05% TFA buffer to afforded the product (105 mg, 81%). m/z (ES) 601(M)+ and 603 (M+2)+, also 623 (MNa)+and 625 (MNa+2)+.

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 Gilson reverse phase HPLC
  7. washeluting with a gradient of 10-90% acetonitrile in water with 0.05% TFA buffer

Quellen und Nachweise

ORD-Eintrag
ord-fb85cf89328449d3bfcfd5aaeae3ff41
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653260B2

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