2'-C-Methylcytidine → HCID 66973176, compound

HRID 1359937Notes

Reaction equation

HRID 1359937 reaction equation
[CH3:1][C@@:2]1([OH:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]1=[O:12].C([Mg]Cl)(C)(C)C.Cl[P:26]([NH:35][C@H:36]([C:38]([O:40][CH:41]([CH2:46][CH2:47][CH3:48])[CH2:42][CH2:43][CH2:44][CH3:45])=[O:39])[CH3:37])([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:27]>C1COCC1>[CH3:37][C@H:36]([NH:35][P:26]([O:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)([O:9][CH2:8][C@H:5]1[O:4][C@@H:3]([N:10]2[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]2=[O:12])[C@:2]([CH3:1])([OH:18])[C@@H:6]1[OH:7])=[O:27])[C:38](=[O:39])[O:40][CH:41]([CH2:46][CH2:47][CH3:48])[CH2:42][CH2:43][CH2:44][CH3:45]

Participants

5

Reactant 3

HCID 5009022'-C-MethylcytidineHCID 86645297HCID 86645297, compoundHCID 178418310HCID 178418310, compound

Product 1

HCID 66973176HCID 66973176, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

2′-C-Methylcytidine was diluted with THF (0.097 M). The resulting slurry was cooled to −78° C., then tert-butylmagnesium chloride (as 1.0 M solution in THF, 2.2 eq.) was added. The mixture was immediately warmed to 0° C., stirred for 30 min and again cooled to −78° C., then propylpentyl N-[chloro(phenyloxy)phosphoryl]-L-alaninate (as 1.0 M solution in THF, 2.2 eq.) was added dropwise. The reaction was allowed to reach RT overnight, and then was quenched by the addition of water. The aqueous phase was extracted three times with EtOAc, the combined organic phases were dried over Na2SO4. The crude product was purified by column chromatography on silica gel (DCM/MeOH 92:8), and the resulting off white solid was dissolved in DMSO and purified by RP-HPLC (stationary phase: column Symmetry C18, 7 μm, 19×300 mm. Mobile phase: acetonitrile/H2O, water buffered with 5 mM AMBIC). Fractions containing the pure diastereoisomers were combined and freeze-dried to afford the title compounds as a white solid.

Workup

  1. temperatureThe mixture was immediately warmed to 0° C.
  2. temperatureagain cooled to −78° C.
  3. waitto reach RT overnight
  4. customwas quenched by the addition of water
  5. extractionThe aqueous phase was extracted three times with EtOAc
  6. dry with materialthe combined organic phases were dried over Na2SO4
  7. customThe crude product was purified by column chromatography on silica gel (DCM/MeOH 92:8)
  8. dissolutionthe resulting off white solid was dissolved in DMSO
  9. custompurified by RP-HPLC (stationary phase: column Symmetry C18, 7 μm, 19×300 mm. Mobile phase: acetonitrile/H2O, water buffered with 5 mM AMBIC)
  10. additionFractions containing the pure diastereoisomers
  11. customfreeze-dried

Sources & evidence

ORD record
ord-f5bc0b0be2a14078926c3eccd6c6dbb6
Source dataset
uspto-grants-2011_02
Patent number
US07879815B2

Reaction notes

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