Tetrahydrofuran → 4-Phthalimido-7-[3,5-di-o-(p-toluoyl)-2-c-methyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

HRID 1391976Notes

Reaction equation

HRID 1391976 reaction equation
O1CCCC1.[H-].[Na+].[C:8]1(=[O:27])[N:12]([C:13]2[C:14]3[CH:21]=[CH:20][NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)[C:11](=[O:22])[C:10]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:9]12.OP([O-])(O)=O.[K+].[C:34]1([CH3:61])[CH:39]=[CH:38][C:37]([C:40]([O:42][C@@H:43]2[C@@H:47]([CH2:48][O:49][C:50]([C:52]3[CH:57]=[CH:56][C:55]([CH3:58])=[CH:54][CH:53]=3)=[O:51])[O:46][C@@H:45]3[O:59][C@:44]23[CH3:60])=[O:41])=[CH:36][CH:35]=1>C(OCC)(=O)C.CN(C)C(=O)C>[C:11]1(=[O:22])[N:12]([C:13]2[C:14]3[CH:21]=[CH:20][N:19]([C@@H:45]4[O:46][C@H:47]([CH2:48][O:49][C:50]([C:52]5[CH:53]=[CH:54][C:55]([CH3:58])=[CH:56][CH:57]=5)=[O:51])[C@@H:43]([O:42][C:40]([C:37]5[CH:38]=[CH:39][C:34]([CH3:61])=[CH:35][CH:36]=5)=[O:41])[C@@:44]4([CH3:60])[OH:59])[C:15]=3[N:16]=[CH:17][N:18]=2)[C:8](=[O:27])[C:9]2=[CH:26][CH:25]=[CH:24][CH:23]=[C:10]12

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 516951Monobasic potassium phosphateHCID 103554262-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dioneHCID 113610461,2-Anhydro-3,5-di-O-(p-toluoyl)-2-C-methyl-alpha-D-ribofuranose

Product 1

HCID 112391664-Phthalimido-7-[3,5-di-o-(p-toluoyl)-2-c-methyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Tetrahydrofuran (5.4 L), sodium hydride (146 g of 60% dispersion in oil, unwashed), and N,N-dimethylacetamide (4 L) were charged to a 72 L flask and the suspension was cooled to 0° C. 4-Phthalimido-7H-pyrrolo[2,3-d]pyrimidine (3-2) (2.08 kg) was added to the reaction while maintaining the temperature below 25° C. N,N-Dimethylacetamide (1.4 L) was added followed by the solution of the epoxide (2.75 assay kg) in toluene from Step A, and the reaction mixture was heated at 50-90° C. for 9 h. After cooling to ambient temperature, ethyl acetate (19 L) and aqueous KH2PO4 (0.97 kg in 19 L of water) were added. The organic phase was washed with water. The resulting organic solution was solvent-switched to toluene by vacuum distillation (T<40° C.) to give a final volume of 10 L.

Workup

  1. temperaturewhile maintaining the temperature below 25° C
  2. temperaturethe reaction mixture was heated at 50-90° C. for 9 h
  3. temperatureAfter cooling to ambient temperature
  4. washThe organic phase was washed with water
  5. distillationby vacuum distillation (T<40° C.)
  6. customto give a final volume of 10 L

Sources & evidence

ORD record
ord-a996a8e645eb4672875b19dcdabc7c43
Source dataset
uspto-grants-2008_03
Patent number
US07339054B2

Reaction notes

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