Nitrogen → 5-(5-Formylthien-2-yl)-uridine

HRID 1475129Notes

Reaction equation

HRID 1475129 reaction equation
I[C:2]1[C:3](=[O:18])[NH:4][C:5](=[O:17])[N:6]([CH:16]=1)[C@@H:7]1[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[C@H:8]1[OH:9].[CH:19]([C:21]1[S:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20].C([O-])([O-])=O.[Cs+].[Cs+].N#N.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+]>>[CH:19]([C:21]1[S:25][C:24]([C:2]2[C:3](=[O:18])[NH:4][C:5](=[O:17])[N:6]([CH:16]=2)[C@@H:7]2[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[C@H:8]2[OH:9])=[CH:23][CH:22]=1)=[O:20]

Participants

6

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 12681085-IodouridineHCID 27734305-Formyl-2-thiopheneboronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)

Product 1

HCID 866699805-(5-Formylthien-2-yl)-uridineYield 23%

Conditions

Temperature
60 °C

Procedure

A 2-necked round bottom flask with 5-iodouridine (100 mg, 270 μmol), 5-formyl-2-thiopheneboronic acid (1.5 eq) and Cs2CO3 (2 eq.) was purged with N2. Upon addition of TPPTS (0.0625 eq.), Na2Cl4Pd (0.025 eq.) and degassed H2O (5 mL) the mixture turned orange in colour. The reaction was stirred under N2 for 1 h at 60° C., turning brown/black. Once the starting material was fully consumed, the reaction mixture was cooled to room temperature. The pH was adjusted to 7 with HCl 1% and the reaction mixture was filtered through Celite. The solvents were removed to give a colourless powder. After purification, the title compound was obtained in 23% yield (16 mg). δH (400 MHz, DMSO-d6) 3.65-3.85 (2H, m, H-5′), 3.90-3.95 (1H, m, H-4′), 4.02-4.17 (2H, m, H-2′ and H-3′), 5.11 (1H, d, J=5.9 Hz, OH-3′), 5.54 (1H, d, J=5.0 Hz, OH-2′), 5.60 (1H, t, J=4.3 Hz, OH-5′), 5.80 (1H, d, J=3.0 Hz, H-1′), 7.56 (1H, d, J=4.1 Hz, Th), 7.93 (1H, d, J=4.0 Hz, Th), 9.02 (1H, s, H-6), 9.87 (1H, s, CHO), 11.9 (1H, s, NH); δC (75.5 MHz, DMSO-d6) 59.6 (C-5′), 68.7 (C-3′), 74.5 (C-2′), 84.4 (C-4′), 89.5 (C-1′), 106.9 (C-5), 122.9, 137.3, 138.7, 141.6, 144.4, 149.4 (C-2+C-6+C—Th), 161.4 (C-4), 184.3 (CHO). m/z (ESI) 353.0448 [M−H]−, C14H13O7N2S requires 353.0449.

Workup

  1. customdegassed H2O (5 mL) the mixture
  2. customOnce the starting material was fully consumed
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationthe reaction mixture was filtered through Celite
  5. customThe solvents were removed
  6. customto give a colourless powder
  7. customAfter purification

Sources & evidence

ORD record
ord-d75953424452459f975edc295b1dd396
Source dataset
uspto-grants-2015_04
Patent number
US09018370B2

Reaction notes

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