Trimethylsilyl triflate → [(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-4-methyloxolan-2-yl]methyl benzoate

HRID 633783Notes

Reaction equation

HRID 633783 reaction equation
[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:12][C@@:13]1([O:46][C:47](=[O:54])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C@H:26]([O:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C@@H:25]([CH2:36][O:37][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:24][C@H:14]1OC(=O)C1C=CC=CC=1.C1CCN2C(=NCCC2)CC1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>CC#N.CCOC(C)=O>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:14]3[O:24][C@H:25]([CH2:36][O:37][C:38](=[O:45])[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C@@H:26]([O:27][C:28](=[O:35])[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C@@:13]3([CH3:12])[O:46][C:47](=[O:54])[C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 108755601,2,3,5-Tetra-O-benzoyl-2-C-methyl-beta-D-ribofuranoseHCID 148092816-Chloro-7-iodo-7-deazapurine

Product 1

HCID 89779566[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-4-methyloxolan-2-yl]methyl benzoateYield 48.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine 8 (903 mg, 3.23 mmol), 2-C-methyl-1,2,3,5-tetra-O-benzoyl-β-D-ribofuranose 9 (1.7 g, 2.93 mmol) and DBU (1.3 ml, 8.69 mmol) in MeCN (20 ml) was dropwise added TMSOTf (2.1 ml, 11.62 mmol) at 0° C. and the mixture was then stirred at 70° C. for 22.5 h. After cooling, the mixture was diluted with AcOEt (100 ml), washed with aq NaHCO3 (sat., 25 ml), water (25 ml) and brine (25 ml). The organic layer was dried over MgSO4 and evaporated. The residue was chromatographed on silica (hexanes/toluene, 1:1; then hexanes/toluene/MeCN, 49:49:2→3:3:4) affording title compound 10 as a white foam (1.04 g, 48%). Compound was recrystallized from EtOH. Mp 95° C. [α]20D −69.3 (c 0.280, CHCl3). 1H NMR (500 MHz, CDCl3): 1.59 (s, 3H, CH3); 4.72 (td, 1H, J4′,3′=J4′,5′b=5.8, J4′,5′a=3.4, H-4′); 4.85 (dd, 1H, Jgem=12.2, J5′b,4′=5.8, H-5′b); 4.95 (dd, 1H, Jgem=12.2, J5′a,4′=3.4, H-5′a); 6.03 (d, 1H, J3′,4′=5.8, H-3′); 6.95 (s, 1H, H-1′); 7.34, 7.46 and 7.47 (3×m, 3×2H, H-m-Bz); 7.54, 7.59 and 7.61 (3×m, 3×1H, H-p-Bz); 7.69 (s, 1H, H-6); 7.96, 8.10 and 8.11 (3×m, 3×2H, H-o-Bz); 8.75 (s, 1H, H-2). 13C NMR (125.7 MHz, CDCl3): 17.92 (CH3); 52.68 (C-5); 63.33 (CH2-5′); 75.55 (CH-3′); 80.04 (CH-4′); 84.93 (C-2′); 88.95 (CH-1′); 117.71 (C-4a); 128.49, 128.54 and 128.63 (CH-m-Bz); 128.65, 129.50 and 129.61 (C-i-Bz); 129.78, 129.83 and 129.92 (CH-o-Bz); 132.66 (CH-6); 133.38, 133.66, 133.72 (CH-p-Bz); 150.68 (C-7a); 151.17 (CH-2); 153.15 (C-4); 165.09, 165.33 and 166.32 (CO). IR (CHCl3): 3092, 3066, 3034, 1727, 1602, 1587, 1577, 1538, 1504, 1493, 1451, 1444, 1339, 1316, 1269, 1248, 1178, 1162, 1141, 1116, 1070, 1027, 1002, 952, 943, 843, 822, 725, 712, 686, 617, 600. MS (FAB): m/z 738 (M+H). HRMS (FAB) for C33H26ClIN3O7 [M+H] calcd: 738.0504. found: 738.0491. Anal. Calcd for C33H25ClIN3O7: C, 53.71; H, 3.41; N, 5.69. Found: C, 53.91; H, 3.29; N, 5.38.

Workup

  1. customat 0° C.
  2. temperatureAfter cooling
  3. washwashed with aq NaHCO3 (sat., 25 ml), water (25 ml) and brine (25 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. customevaporated
  6. customThe residue was chromatographed on silica (hexanes/toluene, 1:1

Sources & evidence

ORD record
ord-4de1c0555f14468695df8b6d4c41cc1d
Source dataset
uspto-grants-2016_04
Patent number
US09321800B2

Reaction notes

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