1H-imidazole-2-carbaldehyde → (S)-5-(5-(1-(((1H-imidazol-2-yl)methyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile

HRID 1891475Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1891475
Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[NH:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH:34]=O.[BH4-].[Na+]>CO.C(O)(=O)C>[NH:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH2:34][NH:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1

Komponenten

6

Edukt 3

HCID 249551H-imidazole-2-carbaldehydeHCID 4311764Sodium borohydrideHCID 67193845(S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride

Produkt 1

HCID 53232432(S)-5-(5-(1-(((1H-imidazol-2-yl)methyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrileAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

Prepared using General Procedure 11. To (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (25 mg, 0.06 mmol) and 1H-imidazole-2-carbaldehyde (6.4 mg, 0.06 mmol) in anhydrous MeOH (1 mL) was added acetic acid (1 drop). The solution was stirred at 55° C. for 3 h before cooling to room temperature and the addition of NaBH4 (4.6 mg, 0.12 mmol). The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with water (0.5 mL) and partitioned between EA (5 mL) and water (5 mL). The organic layers washed with water and brine, and the product purified by preparative HPLC to afford 22 mg (81%) of (S)-5-(5-(1-(((1H-imidazol-2-yl)methyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile 28 as half-white solid. LCMS-ESI (m/z) calculated for C25H24N6OS: 456.2; found 457.2 [M+H]+, tR=2.38 min.

Aufarbeitung

  1. customPrepared
  2. temperaturebefore cooling to room temperature
  3. stirringThe mixture was stirred at room temperature for 12 h
  4. customThe reaction mixture was quenched with water (0.5 mL)
  5. custompartitioned between EA (5 mL) and water (5 mL)
  6. washThe organic layers washed with water and brine
  7. customthe product purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-1159e38ae56c486aae46351828009d80
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08507538B2

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