Reaktion #317205

Reaktionsgleichung

HCl

N-methylbenzene-1,2-diamine

DIEA

methyl 1-[(trans-4-tert-butylcyclohexyl)amino]indane-5-carboxylate

DIEA

thiophosgene

→

methyl 1-[(trans-4-tert-butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]indane-5-carboxylate

Lösungsmittel

dichloromethane

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITat room temperature for 45 min
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 1 h at room temperature
3. 3
   SonstigeThe organic layer was separated
4. 4
   Waschenwashed with aqueous HCl (1N, 30 mL), saturated aqueous NaHCO3 (30 mL), brine (30 mL)
5. 5
   Trocknendried over Na2SO4
6. 6
   Einengenconcentrated to dryness
7. 7
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane (30 mL)
8. 8
   workup.STIRRINGThe reaction mixture was stirred for 30 min at room temperature
9. 9
   Filtrationfiltered through Celite
10. 10
    WaschenThe organic solution was washed once with saturated NaHCO3 (30 mL)
11. 11
    Trocknendried over Na2SO4
12. 12
    Einengenconcentrated

Vorschrift

To a 0° C. solution of methyl 1-[(trans-4-tert-butylcyclohexyl)amino]indane-5-carboxylate (0.43 g, 1.30 mmol) and DIEA (0.27 mL, 1.56 mmol) in dry dichloromethane (20 mL) was added thiophosgene (0.11 mL, 1.36 mmol) slowly. After stirring at 0° C. for 10 min and then at room temperature for 45 min, a solution of N-methylbenzene-1,2-diamine (0.38 g, 3.12 mmol) and DIEA (0.53 mL, 3.12 mmol) in dry dichloromethane (5 mL) was added. The reaction mixture was stirred for 1 h at room temperature, then diluted with dichloromethane (30 mL) and poured into aqueous HCl (1N, 30 mL). The organic layer was separated and washed with aqueous HCl (1N, 30 mL), saturated aqueous NaHCO3 (30 mL), brine (30 mL), dried over Na2SO4 and then concentrated to dryness. The residue was dissolved in dichloromethane (30 mL) and mercury (II) trifluoroacetate (0.61 g, 1.43 mmol) was added. The reaction mixture was stirred for 30 min at room temperature and then filtered through Celite. The organic solution was washed once with saturated NaHCO3 (30 mL), dried over Na2SO4 and concentrated. Chromatography (15% EtOAc in Hexane) afforded methyl 1-[(trans-4-tert-butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]indane-5-carboxylate. HPLC/MS: m/z=460.3 (M+1), Rt=3.46 min. 1H NMR (CDCl3): δ 7.85 (1H, s), 7.78 (1H, d, J=8.0 Hz), 7.71 (1H, m), 7.27 (1H, d, J=8.5 Hz), 7.25-7.18 (3H, m), 5.04 (1H, dd, J=7.5, 5.0 Hz), 3.90 (3H, s), 3.48 (3H, s), 3.24 (1H, m), 3.10 (1H, m), 2.83 (1H,

Quelle