Pyridine → HCID 86750100, compound

HRID 1082095Notes

Reaction equation

HRID 1082095 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:20][N:21]2[CH2:25][CH2:24][CH2:23][CH:22]2[O:26][CH2:27][CH3:28])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@H:9]1[O:17][C@H:14]([CH2:15]O)[C@@H:12]([OH:13])[C@H:10]1[OH:11].S(Cl)([Cl:31])=O.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(#N)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:20][N:21]2[CH2:25][CH2:24][CH2:23][CH:22]2[O:26][CH2:27][CH3:28])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@H:9]1[O:17][C@H:14]([CH2:15][Cl:31])[C@@H:12]([OH:13])[C@H:10]1[OH:11]

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 86750101HCID 86750101, compound

Product 1

HCID 86750100HCID 86750100, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The title compound was prepared according to general method C. (S)-2-Chloro-N-[2-(methylmethoxy)-1-pyrrolidinyl]adenosine [Knutsen, L. J. S., Lau, J., Sheardown, M. J., Thomsen, C.; Bioorganic and Medicinal Chemistry Letters, 1993, 3, 2661-2666](0.35 g, 0.8 mmol) was dissolved in acetonitrile (5 ml) and cooled on an ice-water bath. Under a nitrogen atmosphere, thionyl chloride (0.34 g, 0.2 ml, 2.4 mmol) (see Borchardt, R. T., Huber, J. A. and Wu, Y. S., Journal of Organic Chemistry, 1976, 41, 565-567) was added and a precipitate appeared which dissolved over the following 15 min. Pyridine (0.13 ml, 0.13 g, 1.6 mmol) was introduced gradually, the reaction mixture became yellow in colour and was allowed to reach room temperature gradually. After stirring the mixture overnight, ice was added and the reaction mixture was neutralised to pH 7 with aqueous sodium bicarbonate prior to extraction with ethyl acetate (2×10 ml). The combined extracts were dried (MgSO4) and evaporated to provide the intermediate 2,3-O-sulphinyl derivative (0.35 g), to which was added methanol (5 ml), water (1 ml) and 25% aqueous ammonia solution (0.25 ml) and this mixture was stirred for 16 h. The solution was evaporated in vacuo, and the resultant residue was purified by flash chromatography on silica gel eluting with a mixture of dichloromethane and 10% ammonia in ethanol (17:3), to provide the title (S)-2,5'-dichloro-5'-deoxy-N-[2-(methylmethoxy)-1-pyrrolidinyl]adenosine (0.12 g, 34%) as a foam, 1H-NMR (400 MHz, DMSO-d6) δ1.50-1.60 (1H, br, pyrrolidine C--H), 1.78 (2H, br q, pyrrolidine C--H), 1.92-2.03 (1H, br, pyrrolidine C--H), 3.85, 3.95 (2H, ABX, H-5'a and H-5'b), 4.09 (1H, br dd, H-4'), 4.17 (1H, dd, H-3'), 4.67 (1H, dd, H-2'), 5.49, 5.62 (2H, 2d, 2'- and 3'-OH), 5.87 (1H, d, H-1'), 8.38 (1H, s, H-8), 9.34 (1H, br s, --NH). HPLC retention time 9.65 min. (gradient elution over 30 min.; 20-80% acetonitrile/0.1% TFA in water, 99% purity at 250 nm). C16H22Cl2N6O4.0.25 H2O requires C, 43.9; H, 5.2; N, 19.2. Found: C, 43.7; H, 5.4; N, 19.4%.

Workup

  1. temperaturecooled on an ice-water bath
  2. addition, Journal of Organic Chemistry, 1976, 41, 565-567) was added
  3. dissolutiondissolved over the following 15 min
  4. customto reach room temperature
  5. additionwas added
  6. extractionto extraction with ethyl acetate (2×10 ml)
  7. dry with materialThe combined extracts were dried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-5aa2226ff92543daab83e5ee19d54eb6
Source dataset
uspto-grants-1996_12
Patent number
US05589467

Reaction notes

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