Triethylamine → 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid

HRID 480107Notes

Reaction equation

HRID 480107 reaction equation
C(O[C:4]([C:6]12[CH2:13][CH2:12][C:9]([C:14]([OH:16])=[O:15])([CH2:10][CH2:11]1)[CH2:8][CH2:7]2)=O)C.Cl.[NH2:18][C:19]1[C:20](=[O:33])[N:21]([CH2:30][CH2:31][CH3:32])[C:22](=[O:29])[N:23]([CH2:26][CH2:27][CH3:28])[C:24]=1[NH2:25].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[K+]>O.CC(O)C.C(#N)C>[O:29]=[C:22]1[N:23]([CH2:26][CH2:27][CH3:28])[C:24]2[N:25]=[C:4]([C:6]34[CH2:7][CH2:8][C:9]([C:14]([OH:16])=[O:15])([CH2:10][CH2:11]3)[CH2:12][CH2:13]4)[NH:18][C:19]=2[C:20](=[O:33])[N:21]1[CH2:30][CH2:31][CH3:32]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 3011324-(Ethoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 187676182,4(1H,3H)-Pyrimidinedione, 5,6-diamino-1,3-dipropyl-, hydrochloride (1:1)

Product 1

HCID 98865894-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acidYield 87.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2.00 g (8.84 mmol) of bicyclo[2.2.2]octane-1,4-dicarboxylic acid monoethyl ester, 2.60 g (9.89 mmol) of 5,6-diamino-1,3-dipropyl-1H-pyrimidine-2,4-dione hydrochloride, 5.32 ml (38.1 mmol) of NEt3, and 30 ml anhydrous acetonitrile was added 3.76 g (9.89 mmol) of HATU. The reaction solution was stirred at rt for 1 h. The reaction mixture was concentrated in vacuo and combined with 40-ml EtOAc and 40 ml of 10% citric acid. The aqueous layer was separated and washed twice with 40-ml portions of EtOAc. The combined organic fractions were washed with 20-ml portions of sat'd NaHCO3 and brine and conc'd in vacuo. The resultant solid was combined, in a 200-ml round-bottom flask equipped with a condenser, with a mixture of 35 ml of i-PrOH and 35 ml of 1 N KOH (35 mmol) and heated to reflux. After heating for 1 hour, the reaction solution was conc'd in vacuo, taken up in 40 ml of water, and washed twice with 30-ml portions of CH2Cl2. The aqueous layer was acidified with conc'd HCl and the resultant precipitate collected by suction filtration to give 3.00 g (87% yield) of an off-white solid. (MH+=389.25)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe aqueous layer was separated
  3. washwashed twice with 40-ml portions of EtOAc
  4. washThe combined organic fractions were washed with 20-ml portions of sat'd NaHCO3 and brine and conc'd in vacuo
  5. customThe resultant solid was combined, in a 200-ml round-bottom flask
  6. temperatureheated to reflux
  7. temperatureAfter heating for 1 hour
  8. washwashed twice with 30-ml portions of CH2Cl2
  9. filtrationthe resultant precipitate collected by suction filtration

Sources & evidence

ORD record
ord-d2e6e3a8354041998bef48e279b38e17
Source dataset
uspto-grants-2003_11
Patent number
US06649600B1

Reaction notes

Loading…