Phosphoric Acid → (1r,cis)-4-(6-Amino-9h-purin-9-yl)-2-cyclopentene-1-methanol o-diphosphate

HRID 1241360Notes

Reaction equation

HRID 1241360 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[CH2:15][C@@H:14]([CH2:16][OH:17])[CH:13]=[CH:12]1.[P:18](Cl)(Cl)(Cl)=[O:19].[P:23](=[O:27])([OH:26])([OH:25])[OH:24].C(N(CCCC)CCCC)CCC.C(=O)([O-])[OH:42].C([NH+](CC)CC)C.CCN(CCO)CC>P(OC)(OC)(OC)=O.CN(C)C=O.O>[P:18]([O:17][CH2:16][C@@H:14]1[CH2:15][C@H:11]([N:6]2[CH:5]=[N:4][C:3]3[C:7]2=[N:8][CH:9]=[N:10][C:2]=3[NH2:1])[CH:12]=[CH:13]1)([O:27][P:23]([OH:26])([OH:25])=[O:24])(=[O:19])[OH:42]

Participants

10

Reactant 6

HCID 1004Phosphoric AcidHCID 7497DiethylethanolamineHCID 7622Tributylamine2×HCID 24813Phosphorus oxychlorideHCID 466400[(1R,4S)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]methanolHCID 11768884Triethylammonium hydrogen carbonate

Product 1

HCID 21059623(1r,cis)-4-(6-Amino-9h-purin-9-yl)-2-cyclopentene-1-methanol o-diphosphateYield 37%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 10541Trimethyl PhosphateSolvent

Conditions

Temperature
0 °C

Procedure

The title molecule was prepared by a modification of the method of Broom (Mishra, N. C. and Broom, A. D., J. Chem. Soc., Chem. Commun., 1991, 1276). (1R,cis)-4-(6-Amino-9H-purin-9-yl)-2-cyclopentene-1-methanol (Example 1, 231 mg, 1.0 mmol) was dissolved in trimethyl phosphate (5 mL). Phosphoryl chloride (0.27 mL, 3.0 mmol) was added to the stirred, cooled (0° C.) solution. After 3 hours, a solution of 86% phosphoric acid (1.14 g, 10 mmol) and tri-n-butylamine (2.4 mL, 10 mmol) in dimethyformamide (15 mL) was added to the cold (0° C.) stirring solution, followed immediately by tri-n-butylamine (3 mL). After 1 minute, 1 M triethylammonium hydrogen carbonate buffer (100 mL) was added and stirring was continued for 30 minutes. The reaction solution was diluted to 3 L with deionized water and applied to a 1.1×7.0 cm DEAE Sepahadex A25 (Aldrich) ion exchange chromatography column which had been washed with 1.0 M ammonium bicarbonate and preequilibrated with deionized water. The title compound was eluted with a 0 to 0.5 M gradient (4 L) of ammonium bicarbonate. The appropriate fractions were combined and the volatiles removed by evaporation in vacuo, redissolved in water and evaporated again to give the ammonium salt of the title compound (0.37 mmol, 37%); UV (0.1 M HCl)λ max=260 nm. UV purity (254 nm detection) was 100% by analytical strong anion exchange HPLC (Whatman Partisil 5, SAX RAC II, 0.05 M to 0.95 M gradient with ammonium phosphate buffer (pH 5.5), 5% methanol). 1H-NMR (D2O) δ 8.06 (s, 1H), 8.05 (s, 1H), 6.13–6.21 (m, 1H), 5.82–5.88 (m, 1H), 5.45–5.53 (m, 1H), 3.76–3.90 (m, 2H), 3.02–3.16 (br m, 1H), 2.64–2.78 (m, 1H), 1.52–1.64 (m, 1H); 31P-NMR (D2O) −9.90 (d, 1P, J=20.3 Hz), −10.84 (d, 1P, J=20.3). Mass spectrum (ES−) m/e 390 (M−H).

Workup

  1. customThe title molecule was prepared by a modification of the method of Broom (Mishra, N
  2. waitAfter 1 minute
  3. stirringstirring
  4. waitwas continued for 30 minutes
  5. washhad been washed with 1.0 M ammonium bicarbonate
  6. washThe title compound was eluted with a 0 to 0.5 M gradient (4 L) of ammonium bicarbonate
  7. customthe volatiles removed by evaporation in vacuo
  8. dissolutionredissolved in water
  9. customevaporated again

Sources & evidence

ORD record
ord-73ebcd20ef034dffbb214af699426c4c
Source dataset
uspto-grants-2006_10
Patent number
US07115590B1

Reaction notes

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