Ammonia → 3-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionamide

HRID 480148Notes

Reaction equation

HRID 480148 reaction equation
[O:1]=[C:2]1[N:10]([CH2:11][CH2:12][CH3:13])[C:9]2[N:8]=[C:7]([C:14]34[CH2:21][CH2:20][C:17]([CH2:22][CH2:23][C:24]([OH:26])=O)([CH2:18][CH2:19]3)[CH2:16][CH2:15]4)[NH:6][C:5]=2[C:4](=[O:27])[N:3]1[CH2:28][CH2:29][CH3:30].C[N:32](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N>CN(C=O)C>[O:1]=[C:2]1[N:10]([CH2:11][CH2:12][CH3:13])[C:9]2[N:8]=[C:7]([C:14]34[CH2:21][CH2:20][C:17]([CH2:22][CH2:23][C:24]([NH2:32])=[O:26])([CH2:16][CH2:15]3)[CH2:18][CH2:19]4)[NH:6][C:5]=2[C:4](=[O:27])[N:3]1[CH2:28][CH2:29][CH3:30]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 216466TonapofyllineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 187676873-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]oct-1-yl]-propionamideYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo-[2.2.2]oct-1-yl]-propionic acid (510 mg, 1.22 mmol) and HATU (1.1 eq, 1.34 mmol, 511 mg) in DMF (10 ml) was added Hunig's base (1.3 eq, 1.60 mmol, 205 mg). After the resulting suspension had been stirred for 1 h, excess ammonia (0.5 M in dioxane, 4.0 ml) was added and the mixture was stirred overnight (14 h). The solvent was removed in vacuo and the resulting residue was partitioned between CH2Cl2 (10 ml) and 1 N HCl (10 ml) with the aid of 2 ml MeOH to assist in the transfer and improve solubility. The aqueous phase was extracted with CH2Cl2 (2×10 ml), the combined organic phases were washed with 1 N HCl (2×10 ml), dried (MgSO4), filtered and evaporated in vacuo to give an off-white solid (455 mg, 90%). MS: 416 (MH+).

Workup

  1. stirringthe mixture was stirred overnight (14 h)
  2. customThe solvent was removed in vacuo
  3. customthe resulting residue was partitioned between CH2Cl2 (10 ml) and 1 N HCl (10 ml) with the aid of 2 ml MeOH
  4. extractionThe aqueous phase was extracted with CH2Cl2 (2×10 ml)
  5. washthe combined organic phases were washed with 1 N HCl (2×10 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-9c22843f8f1948579b858c93766c4b5a
Source dataset
uspto-grants-2003_11
Patent number
US06649600B1

Reaction notes

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