Thymidine → HCID 18658254, compound

HRID 323526Notes

Reaction equation

HRID 323526 reaction equation
[C:1]([C@@H:3]1[C@@H:7]([CH2:8][O:9][C:10]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:6][C@@H:5]([N:29]2[CH:36]=[CH:35][C:33](=[O:34])[NH:32][C:30]2=[O:31])[CH2:4]1)#N.[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H]([OH:40])C1.CC(C[AlH]CC(C)C)C>C1COCC1.C1(C)C=CC=CC=1>[C:10]([O:9][CH2:8][C@H:7]1[O:6][C@@H:5]([N:29]2[CH:36]=[CH:35][C:33](=[O:34])[NH:32][C:30]2=[O:31])[CH2:4][C@@H:3]1[CH:1]=[O:40])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 5789ThymidineHCID 14487Diisobutylaluminum hydrideHCID 18658249HCID 18658249, compound

Product 1

HCID 18658254HCID 18658254, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3′- cyano-2′,3′-dideoxy-5′-O-trityluridine (0.96 g, 2 mmol), (prepared in a manner equivalent to that of the thymidine analog above) in dry THF (20 ml) under argon, was added a solution of DIBAL-H in toluene (Aldrich) (1M, 4 ml) at −10° C. over a period of 10 min. After 30 mins the reaction was quenched with MeOH (5 ml) at −10° C. The mixture was further stirred at ambient temperature for 30 mins and diluted with CH2Cl2 (25 ml) before concentrating under vacuum. This process was repeated with CH2Cl2 (3×25 ml) in order to remove the residual THF. The residue was purified by flash chromatography on silica gel (25 g). Elution with CH2Cl2 (9:1, v/v) and crystallization from CH2Cl2/MeOH gave 5′-O-trityl-3′-C-formyl-2′,3′-dideoxyuridine (0.53 g, 53%); mp 100° C.; 1H NMR (CDCl3) δ 2.25-2.8 (m, 2, CH2), 3.4 (m, 1, C3′H), 3.45-3.6 (m, 2, C5′CH2), 4.37 (m, 1, C4′H) 5.4 (d, 1, C5H), 6.1 (m, 1, C1′H), 7.2-7.4 (m, 15, C6H5), 7.81 (d, 1, C6H), 7.95 (br s, 1, NH), 9.61 (s, 1, HC═O).

Workup

  1. customAfter 30 mins the reaction was quenched with MeOH (5 ml) at −10° C
  2. additiondiluted with CH2Cl2 (25 ml)
  3. concentrationbefore concentrating under vacuum
  4. customto remove the residual THF
  5. customThe residue was purified by flash chromatography on silica gel (25 g)
  6. washElution with CH2Cl2 (9:1
  7. customv/v) and crystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-f868442391e042d7ac5975a911ce1ec8
Source dataset
uspto-grants-2001_04
Patent number
US06214551B1

Reaction notes

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