Reaktion #2033203

Reaktionsgleichung

2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

4-azetidin-3-ylpiperazin-2-one

DCE

sodium triacetoxyborohydride

→

4-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)piperazin-2-one

Lösungsmittel

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationthen filtered through celite
2. 2
   Waschenwashing with DCM
3. 3
   WaschenThe organic phase was washed with brine (×1)
4. 4
   Einengenconcentrated in vacuo
5. 5
   TrocknenThe organic phase was dried (Na2SO4)
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigeThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-7%)
8. 8
   Waschenwas washed with MeOH/DCM
9. 9
   Waschenthe product eluted with 2M NH3/MeOH affording 514 as a yellow foam (42 mg, 31%)
10. 10
    SonstigeRT 2.28 min [M+H]+ 531.2

Vorschrift

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.26 mmol), 4-azetidin-3-ylpiperazin-2-one (44 mg, 0.28 mmol) and 4 Å powdered molecular sieves (250 mg) in MeOH (2 mL) and DCE (5 mL) was stirred at room temperature for 2 h before the addition of sodium triacetoxyborohydride (108 mg, 0.51 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-7%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 514 as a yellow foam (42 mg, 31%). LCMS (Method I): RT 2.28 min [M+H]+ 531.2. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.79-7.74 (m, 1 H); 7.31-7.24 (m, 2 H); 5.93 (bs, 1 H); 4.35 (m, 4 H); 3.94 (s, 2 H); 3.94-3.80 (m, 7 H); 3.66 (bs, 2 H); 3.43-3.33 (m, 4 H); 3.21 (s, 3 H); 3.06 (s, 2 H); 2.58 (t, J=5.37 Hz, 2 H) and 1.45 (t, J=7.5 Hz, 3 H)

Quelle