64% |
With sodium carbonate;palladium diacetate; In water; acetonitrile; at 100℃; for 5h; |
To an argon purged mixture of free riboside 4 (100 mg, 0.35 mM), IH- pyrazole-5-boronic acid (47 mg, 0.42 mM), Na2(COs)2 (111 mg, 1.06 mM) is added a pre-prepared solution of Pd(OAc)2 (4 mg, 0.018 mM) and TPPTS (25 <n="82"/>mg, 0.044 niM) in water/CH3CN (2:1, 3 mL). The reaction mixture is stirred at 100°C for 5 h. After cooling the mixture is neutralized by the addition of aqueous HCl (3M sol.) and purified by reverse phase chromatography affording product 3q (71 mg, 64percent) as amorphous glassy solid. Compound is lyophylized. 1H NMR (600 MHz, DMSO-J6): 3.56 (ddd, IH, Jgem= 11.9, J5-b,oH= 5.7, J5-M'= 4.0, H-5'b); 3.63 (ddd, IH, Jgem= 11.9, J5-a,oH= 5.1, J5-^4-= 4.0, H-5'a); 3.93 (td, IH, J4<,5.= 4.0, J4-,3-= 3.4, H-4'); 4.13 (ddd, IH, J3-,2-= 5.1, J3,0H= 4.9, J3- A-= 3.4, H-3'); 4.45 (td, IK, Jtau,v= JT1OH= 6.2, J2-,3- = 5.1, H-2'); 5.11 (dd, lH, J0H,5- = 5.7, 5.1, OH-5'); 5.19 (d, IH, Joty- 4.9, OH-3') 5.39 (d, IH, JOu,r= 6.2, OHT); 6.24 (d, IH, Jva>= 6.2, H-I '); 7.07 (s, IH, H-4-pyrazolyl); 7.21 (d, IH, J5>6 = 3.5, H-5); 7.86 (d, IH, J6,5 = 3.5, H-6); 7.93 (s, IH, H-3-pyrazolyl); 8.79 (s, IH, H-2); 13.40 (s, IH5 NH). 13C NMR (151 MHz, DMSO-J6): 61.83 (CH2-5'); 70.84 (CH-3'); 74.23 (CH-2'); 85.35 (CH-4'); 86.87 (CH-I '); 102.79 (CH-5); 105.17 (CH-4-pyrazolyl); 114.28 (C-4a); 127.58 (CH-6); 130.02 (CH-3- pyrazolyl); 150.70 (C-5-pyrazolyl); 150.92 (C-4); 151.15 (CH-2); 152.10 (C- 7a);. MS FAB, mlz (rel. percent): 318 (100)[M+H]. HR MS (FAB): calcd for C14H16N5O4 [M+H] 318.1202, found 318.1200. Anal. Calcd for C14H15N5O4-H2O: C, 50.15; H, 5.11; N, 20.89. Found: C, 50.04; H, 4.92; N, 20.55. |