Ammonia → 5'-Methylspiro[chromane-4,2'-imidazole]-4',6-diamine

HRID 539280

Reaktionsgleichung

Reaktionsgleichung von HRID 539280
Br[C:2]1[CH:3]=[C:4]2[C:11]3([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]3)[CH2:10][CH2:9][O:8][C:5]2=[CH:6][CH:7]=1.O[C@H]1C[NH:22][C@H](C(O)=O)C1.C([O-])([O-])=O.[K+].[K+].N>CS(C)=O.O.[Cu]I>[CH3:17][C:13]1[C:14]([NH2:16])=[N:15][C:11]2([C:4]3[C:5](=[CH:6][CH:7]=[C:2]([NH2:22])[CH:3]=3)[O:8][CH2:9][CH2:10]2)[N:12]=1

Komponenten

8

Edukt 4

HCID 222AmmoniaHCID 5810L-HydroxyprolineHCID 11430Potassium CarbonateHCID 679796056-Bromo-5'-methylspiro[chromane-4,2'-imidazol]-4'-amine2×

Produkt 1

HCID 679794075'-Methylspiro[chromane-4,2'-imidazole]-4',6-diamineAusbeute 65,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittel2×HCID 962WaterLösungsmittel2×

Versuchsvorschrift

A mixture of 6-bromo-5′-methylspiro[chroman-4,2′-imidazol]-4′-amine (Intermediate 4, 115 mg, 0.39 mmol), trans-4-hydroxy-L-proline (51 mg, 0.39 mmol), CuI (37 mg, 0.20 mmol), and K2CO3 (162 mg, 1.17 mmol) in DMSO (0.9 mL) was stirred at r.t. for 15 min. Ammonia, (30-33% in H2O, 0.37 mL, 5.86 mmol) was added and the mixture was subjected to microwave irradiation at 110° C. for 3 h. The mixture was diluted with DMSO and water and filtered through a pad of diatomaceous earth. NaCl (s) was added and the aqueous mixture was extracted with EtOAc (5×35 mL). The combined organic phases were dried (Na2SO4) and evaporated to give a crude product which was purified by flash chromatography (4 g silica, eluent: CHCl3/(MeOH/NH3) gradient) affording the title compound (59 mg, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.76-1.92 (m, 2 H), 2.19 (s, 3 H), 4.18-4.34 (m, 2 H), 4.45 (br. s., 2H), 5.69 (d, 1 H), 6.35 (dd, 1 H), 6.45 (br. s., 2 H), 6.50 (d, 1 H); MS (ES−) m/z 231 [M+H]+.

Aufarbeitung

  1. customirradiation at 110° C. for 3 h
  2. filtrationfiltered through a pad of diatomaceous earth
  3. additionNaCl (s) was added
  4. extractionthe aqueous mixture was extracted with EtOAc (5×35 mL)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. customevaporated
  7. customto give a crude product which
  8. customwas purified by flash chromatography (4 g silica, eluent: CHCl3/(MeOH/NH3) gradient)

Quellen und Nachweise

ORD-Eintrag
ord-e8737551b14e47c5a95bf71821eb6a94
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865911B2

Verknüpfte Notizen

Wird geladen…