Acetic Acid → HCID 131719480, compound

HRID 1077544Notes

Reaction equation

HRID 1077544 reaction equation
[C:1]([OH:4])(=[O:3])[CH3:2].C(O)(=O)C.C(O)(=O)C.[NH2:13][C:14]1([C:20]([O:22][CH2:23][CH:24](OCN2C=NC3C(=O)NC(N)=NC2=3)[CH2:25][O:26]C(C2(N)CCCCC2)=O)=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C(O)(=O)C.[OH-].[NH4+]>O>[C:1]([OH:4])(=[O:3])[CH3:2].[NH2:13][C:14]1([C:20]([O:22][CH2:23][CH2:24][CH2:25][OH:26])=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 176Acetic Acid2×HCID 14923Ammonium HydroxideHCID 137226526HCID 137226526, compound

Product 1

HCID 131719480HCID 131719480, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-((2-Amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy)-1,3-propanediyl bis-(1-amino-cyclohexane-carboxylate) tris acetate, 98 mg (lyophilized sample contained 3.0 equivalents of acetic acid by NMR), 0.143 mmol (=a total of 0.43 mmol of acetic acid) is dissolved in de-ionized water, 0.4 mL, and 38 μL of a 0.015M ammonium hydroxide solution (=0.57 mmol) is added. The mixture is left at room temperature for 7 hrs., the vial is placed in a oil bath maintained at 48°-50° C. and left in the oil bath for 22 hrs. The sample is injected in two equal lots onto a preparative reverse phase HPLC column (YMC-Pack, ODS-AM DM-33-5, 20×250 mm; YMC Inc.). Separation is achieved with a solvent system of 15% methanol/85% 0.1M ammonium acetate buffered to pH 4 with acetic acid, flow rate: 9.5 mL/min and the detector set to 256 nm. The peak representing the mono ester is collected. The solvent is removed under high vacuum to about 2 mL and the residue is lyophilized three times from water containing acetic acid (0.1%) to remove the buffer. Excess acetic acid is then removed by drying at room temperature under high vacuum for 42 hrs. 30 mg (0.068 mmol=48%) of 2-(2-amino-1,6-dihydro-6-oxo purin-9-yl)methoxy)-3-hydroxy-1-propanyl (1-amino-cyclohexane-carboxylate) acetate, identical by HPLC and NMR with the product of Example 4B, is obtained.

Workup

  1. custom, the vial is placed in a oil bath
  2. temperaturemaintained at 48°-50° C.
  3. waitleft in the oil bath for 22 hrs
  4. customSeparation
  5. customis collected
  6. customThe solvent is removed under high vacuum to about 2 mL
  7. additioncontaining acetic acid (0.1%)
  8. customto remove the buffer
  9. customExcess acetic acid is then removed
  10. customby drying at room temperature under high vacuum for 42 hrs

Sources & evidence

ORD record
ord-bb73498fd6dd4c9b8318b99abc1ebb86
Source dataset
uspto-grants-1996_08
Patent number
US05543414

Reaction notes

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