Diisopropylcarbodiimide → (S)-2-(3,5-dimethylphenylacetamido)-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide

HRID 71028

Reaktionsgleichung

Reaktionsgleichung von HRID 71028
[NH2:1][CH:2]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[N:18]([CH:19]=2)[C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[S:15]3)=[CH:8][CH:7]=1)=[O:4].[CH3:32][C:33]1[CH:34]=[C:35]([CH2:40][C:41](O)=[O:42])[CH:36]=[C:37]([CH3:39])[CH:38]=1.CC(C)N=C=NC(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:32][C:33]1[CH:34]=[C:35]([CH2:40][C:41]([NH:1][C@@H:2]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)[C:3]([NH:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:13]=[C:14]4[N:18]([CH:19]=3)[C:17]3[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=3[S:15]4)=[CH:8][CH:7]=2)=[O:4])=[O:42])[CH:36]=[C:37]([CH3:39])[CH:38]=1

Komponenten

6

Edukt 3

HCID 12734DiisopropylcarbodiimideHCID 47494952-(3,5-Dimethylphenyl)acetic acidHCID 866804752-amino-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide

Produkt 1

HCID 51038958(S)-2-(3,5-dimethylphenylacetamido)-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

HATU (258 mg, 0.68 mmol) and DIPEA (197 μl, 1.13 mmol) were added to a solution of 4-[(imidazo[2,1-b]benzothiazol-2-yl)]aniline (150 mg, 0.56 mmol) and N-Boc-4-methylphenylalanine (158 mg, 0.56 mmol) in dry THF (11 ml). After 48 h at room temperature the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (DCM containing 1% MeOH) to afford the desired N-Boc derivative that was dissolved in dry DCM (5 ml). TFA (5 ml) was then added and the reaction mixture was stirred at room temperature for 4 hours. Then the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (DCM containing 10% EtOH) to afford 2-amino-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl]-propanamide in nearly quantitative yield. A suspension of 2-amino-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide (150 mg, 0.35 mmol) in dry DCM (4 ml) was then mixed to 3,5-dimethylphenylacetic acid (60.6 mg, 0.37 mmol) and DMAP (21.5 mg, 0.17 mmol). Once the solution was obtained, DIC (83 l, 0.53 mmol) was added. After 4.5 h at room temperature the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (DCM containing 2% EtOH) to afford (S)-2-(3,5-dimethylphenylacetamido)-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide that was further on purified by crystallization in CHCl3 (32% c.y.)

Aufarbeitung

  1. customOnce the solution was obtained
  2. customAfter 4.5 h at room temperature the solvent was removed under reduced pressure
  3. customthe crude mixture was purified by flash chromatography (DCM containing 2% EtOH)

Quellen und Nachweise

ORD-Eintrag
ord-1b81a8668d9a445dadb0018669dee1c9
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822698B2

Verknüpfte Notizen

Wird geladen…