Thymidine → HCID 86741744, compound

HRID 1789327Notes

Reaction equation

HRID 1789327 reaction equation
[C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[CH2:18](N(CC)CC)[CH3:19].CN(C)[CH:27]=[O:28]>>[C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@:3]([CH:18]=[CH:19][CH:27]=[O:28])([OH:4])[CH2:2]1

Participants

4

Reactant 3

HCID 5789ThymidineHCID 6228DimethylformamideHCID 8471Triethylamine

Product 1

HCID 86741744HCID 86741744, compound

Procedure

Thymidine (488 mg, 2 mmol) is dissolved in dimethylformamide (4 ml), triethylamine (280 μl; 2 mmole) is added and the mixture is stirred for 1 hr. then cooled to -78°. Propargyl aldehyde (200 μl; 4 mmole) is added and the mixture is stirred at this temperature for 2 hrs. and then allowed to come to room temperature over a period of 3 hrs. The solvent and triethylamine are removed under reduced pressure at room temperature. The residue is dissolved in methanol and applied to two preparative tic plates (20×20 cm; silica gel, 2 mm thick). The plates are developed with ethyl acetate containing 5% methanol. The desired product has Rf 0.65 and is detected by means of a thiobarbituric acid coloration test (pink). The starting material has an Rf of 0.4. Removal of the appropriate band from the plates, followed by extraction with methanol affords the title compound as an almost colorless glass (220 mg, 35%) which crystallized on standing m.p. 121°-2°. The infrared spectrum shows bands at 3425 (OH), 1733 (CHO), 1690, 1660, 1295, 1260, 1150, 1095, 1040 cm-1. The NMR spectrum has absorption bands at (DMSO) 1.85 (S, 3H, CH3) 6.19 (t, J=6.1 Hz, 1H, O--CH--N) 7.06 (q,J,=7.8 Hz J2 =14.8 Hz 1H, CH=CH--CHO) 7.95 (s, 1H, 4H) 8.16 (d, J=14.6 Hz, 1H, CH=CH--CHO) 9.60 (d, J=7.8 Hz, 1H, CHO) in addition to the peaks usually observed for thymidine the NH at 11.28 excepted. Mass spectrum m/z (intensity % of base peak), ion: 296 (0.4)M+, 242(2.0) (M-54)+, 180 (4.0) (M-117)+, 117 (100) (M-180)+ , 73 (71)C3H3O.

Workup

  1. temperaturethen cooled to -78°
  2. stirringthe mixture is stirred at this temperature for 2 hrs
  3. waitto come to room temperature over a period of 3 hrs
  4. customThe solvent and triethylamine are removed under reduced pressure at room temperature
  5. dissolutionThe residue is dissolved in methanol
  6. customRemoval of the appropriate band from the plates
  7. extractionfollowed by extraction with methanol

Sources & evidence

ORD record
ord-358b3d5ba0e5479496f40cd68ccde256
Source dataset
uspto-grants-1987_08
Patent number
US04689321

Reaction notes

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