Sodium Carbonate → (2R,3R,4R,5R)-2-(4-amino-5-phenyl-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol

HRID 633785Notes

Reaction equation

HRID 633785 reaction equation
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@@H:12]3[O:18][C@H:17]([CH2:19][OH:20])[C@@H:15]([OH:16])[C@@:13]3([CH3:21])[OH:14])[C:4]=2[N:5]=[CH:6][N:7]=1.[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+].C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+]>O.CC#N.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[C:3]2[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:9][N:8]([C@@H:12]3[O:18][C@H:17]([CH2:19][OH:20])[C@@H:15]([OH:16])[C@@:13]3([CH3:21])[OH:14])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 210697325-iodo-7-(2-C-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 49784204(2R,3R,4R,5R)-2-(4-amino-5-phenyl-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diolYield 70.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

An argon purged mixture of compound 6 from Step 2 (49 mg, 0.12 mmol), phenylboronic acid (25 mg, 0.20 mmol), Na2CO3 (144 mg, 1.36 mmol), TPPTS (15.5 mg, 0.027 mmol) and Pd(OAc)2 (1.4 mg, 6.2 μmol) in water/MeCN (2:1, 1.8 ml) was stirred at 80° C. for 1 h. After cooling, volatiles were removed by evaporation and the residue was purified by reverse phase chromatography (0→100% MeOH in water) affording title compound 7a as white solid (30 mg, 70%). Mp 129° C. [α]20D −55.7 (c 0.226, MeOH). 1H NMR (600 MHz, DMSO-d6): 0.75 (s, 3H, CH3); 3.65 (bdd, 1H, Jgem=12.2, J5′b,4′=2.9, H-5′b); 3.82 (bdd, 1H, Jgem=12.2, J5′a,4′=2.1, H-5′a); 3.86 (ddd, 1H, J4′,3′=9.1, J4′,5′=2.9, 2.1, H-4′); 4.02 (d, 1H, J3′,4′=9.1, H-3′); 5.15 (bs, 3H, OH-2′,3′,5′); 6.10 (bs, 2H, NH2); 6.23 (s, 1H, H-1′); 7.36 (m, 1H, H-p-Ph); 7.44-7.50 (m, 4H, H-o,m-Ph); 7.70 (s, 1H, H-6); 8.16 (s, 1H, H-2). 13C NMR (151 MHz, DMSO-d6): 20.00 (CH3); 59.60 (CH2-5′); 72.01 (CH-3′); 78.88 (C-2′); 82.39 (CH-4′); 90.51 (CH-1′); 100.09 (C-4a); 116.41 (C-5); 120.75 (CH-6); 127.05 (CH-p-Ph); 128.64 (CH-o-Ph); 129.23 (CH-m-Ph); 134.89 (C-i-Ph); 150.67 (C-7a); 151.94 (CH-2); 157.49 (C-4). IR (KBr): 3480, 3431, 3400, 1631, 1622, 1585, 1566, 1537, 1489, 1464, 1445, 1299, 1178, 1123, 1073, 1058, 1029, 799, 763, 705, 550. MS (FAB) m/z 357 (M+H). HRMS (FAB) for C18H21N4O4: [M+H] calcd: 357.1563. found: 357.1557. Anal. Calcd for C18H20N4O4.1.6H2O: C, 56.13; H, 6.07; N, 14.54. Found: C, 56.52; H, 5.74; N, 14.14.

Workup

  1. customAn argon purged
  2. temperatureAfter cooling
  3. customvolatiles were removed by evaporation
  4. customthe residue was purified by reverse phase chromatography (0→100% MeOH in water)

Sources & evidence

ORD record
ord-c5d83350310e450f99596d2fafa69873
Source dataset
uspto-grants-2016_04
Patent number
US09321800B2

Reaction notes

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