Reaktion #598873

Reaktionsgleichung

3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(ethyl)amino)cyclobutyl)propanoic acid

HOAT

HATU

4-tert-butylbenzene-1,2-diamine

→

N-(2-amino-4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(ethyl)amino)cyclobutyl)propanamide

Ausbeute 61.0%

Lösungsmittel

Water

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe mixture was extracted with DCM (30 mL×2)
2. 2
   WaschenThe combined organic phase was washed with H2O (20 mL×2)
3. 3
   TrocknenThe combined organic layers were dried over Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe crude was purified by SGC (DCM: MeOH-70:1-20:1)
7. 7
   Sonstigeto obtain the target (1.6 g, yield: 61%) as a white solid

Vorschrift

To a solution of 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(ethyl)amino)cyclobutyl)propanoic acid (2 g, 4.35 mmol), HOAT (768 mg, 5.65 mmol), HATU (2.2 g, 5.65 mmol) and TEA (3 mL, 21.3 mmol) in DCM (40 mL) was added 4-tert-butylbenzene-1,2-diamine (785 mg, 4.79 mmol) and the mixture was stirred at rt for 2 h. Water (15 mL) was added and the mixture was extracted with DCM (30 mL×2). The combined organic phase was washed with H2O (20 mL×2). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude was purified by SGC (DCM: MeOH-70:1-20:1) to obtain the target (1.6 g, yield: 61%) as a white solid. 1H NMR (500 MHz, MeOD): δH 8.28-8.27 (m, 1H), 8.24-8.23 (m, 1H), 7.10-6.92 (m, 2H), 6.81-6.76 (m, 1H), 6.22 (s, 1H), 5.54-5.52 (m, 1H), 5.03 (s, 1H), 4.36 (s, 1H), 3.03-2.50 (m, 5H), 2.32-2.26 (m, 2H), 2.16-1.80 (m, 4H), 1.73-1.69 (m, 2H), 1.59 (s, 3H), 1.39 (s, 3H), 1.28-1.24 (m, 9H), 0.94-0.85 (m, 3H) ppm; ESI-MS (m/z): 607.3 [M+1]+.

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