Pyridine → HCID 136378400, compound

HRID 1110059Notes

Reaction equation

HRID 1110059 reaction equation
N#N.COC1C=CC(C([NH:24][C:25]2[NH:26][C:27](=[O:65])[C:28]3[N:29]=[CH:30][N:31]([C@@H:34]4[CH2:37][C@H:36]([CH2:38]O)[C@H:35]4[CH2:40][O:41]C(C4C=CC=CC=4)(C4C=CC(OC)=CC=4)C4C=CC(OC)=CC=4)[C:32]=3[N:33]=2)(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1.[ClH:68].[CH3:69][N:70]([CH3:77])[CH2:71][CH2:72][CH2:73][C:74]([OH:76])=[O:75].N1C=CC=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.O.C(OCC)(=O)C.CN(C=O)C>[ClH:68].[CH3:69][N:70]([CH3:77])[CH2:71][CH2:72][CH2:73][C:74]([O:76][CH2:38][C@H:36]1[CH2:37][C@@H:34]([N:31]2[CH:30]=[N:29][C:28]3[C:27](=[O:65])[NH:26][C:25]([NH2:24])=[N:33][C:32]2=3)[C@@H:35]1[CH2:40][OH:41])=[O:75]

Participants

9

Reactant 4

HCID 1049PyridineHCID 10868DicyclohexylcarbodiimideHCID 126916404-(Dimethylamino)butyric acid hydrochlorideHCID 136378402HCID 136378402, compound

Product 1

HCID 136378400HCID 136378400, compoundYield 30.6%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under a stream of argon gas, N2 -(4,4'-dimethoxytrityl)-9-[(1R,2R,3S)-2-(4,4'-dimethoxy-trityl)oxymethyl-3-hydroxymethyl-1-cyclobutyl]-guanine (360 mg, 0.41 mmole), 4-(dimethylamino)-butyric acid hydrochloride (138.7 mg, 0.83 mmole) and 4-(dimethyl-amino)-pyridine (10.1 mg, 0.08 mmole) are dissolved into DMF (4 ml), and then the DMF is distilled off under reduced pressure. The residue is dissolved into DMF (4 ml). Pyridine (0.17 ml, 2.07 mmoles) and dicyclohexyl-carbodiimide (DCC) (170.8 mg, 0.83 mmole) are added thereto, and the resulting mixture is stirred at room temperature overnight. After adding water (4 ml) to the reaction mixture and stirring the mixture for one hour, ethyl acetate and water are added and insoluble matter is filtered off. The filtrate is extracted with ethyl acetate. The extract layer is washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then, volatile substances are distilled off under reduced pressure. 80% acetic acid (30 ml) is added to the residue and stirred overnight. After distilling off the volatile substances from the reaction mixture under reduced pressure, water is added and the water is distilled off. Water is added to the residue and the resulting mixture is washed with ether, after which pH value is adjusted to 9. The solution thus obtained is purified by CM Sephadex column chromatography (water, 0.5M NaCl) and then de-salted by the use of a de-salting apparatus (Microacylizer G-1, mfd. by Asahi Kasei Kogyo) to obtain 9-[(1R,2R,3S)-3-(4-dimethylamino-butyryl)oxymethyl-2-hydroxymethyl-1-cyclobutyl]-guanine hydrochloride (52.0 mg, 30.3%).

Workup

  1. distillationthe DMF is distilled off under reduced pressure
  2. dissolutionThe residue is dissolved into DMF (4 ml)
  3. stirringstirring the mixture for one hour
  4. filtrationinsoluble matter is filtered off
  5. extractionThe filtrate is extracted with ethyl acetate
  6. washThe extract layer is washed with water and saturated aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationThen, volatile substances are distilled off under reduced pressure
  9. addition80% acetic acid (30 ml) is added to the residue
  10. stirringstirred overnight
  11. distillationAfter distilling off the volatile substances from the reaction mixture under reduced pressure, water
  12. additionis added
  13. distillationthe water is distilled off
  14. additionWater is added to the residue
  15. washthe resulting mixture is washed with ether
  16. customThe solution thus obtained
  17. customis purified by CM Sephadex column chromatography (water, 0.5M NaCl)

Sources & evidence

ORD record
ord-04cb3e83e1634ec0a2b211c92409f07d
Source dataset
uspto-grants-1994_06
Patent number
US05324730

Reaction notes

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