Water → 4-[1,3 bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid

HRID 1955633Notes

Reaction equation

HRID 1955633 reaction equation
[CH:1]1([CH2:7][N:8]2[C:15]([NH2:16])=[C:14]([NH2:17])[C:12](=[O:13])[N:11]([CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:9]2=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.NC1N(CC2CCCCC2)C(=O)N(CC2CCCCC2)C(=O)C=1N=O.O.[C:51]([C:54]1[CH:61]=[CH:60][C:57]([CH:58]=O)=[CH:56][CH:55]=1)([OH:53])=[O:52]>CO.[Pd]>[CH:19]1([CH2:18][N:11]2[C:12](=[O:13])[C:14]3[N:17]=[C:58]([C:57]4[CH:60]=[CH:61][C:54]([C:51]([OH:53])=[O:52])=[CH:55][CH:56]=4)[NH:16][C:15]=3[N:8]([CH2:7][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[C:9]2=[O:10])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 962WaterHCID 120884-Formylbenzoic acidHCID 222449706-Amino 1,3-bis(cyclohexylmethyl)-5-nitrosouracilHCID 222449751,3-Bis(cyclohexylmethyl)-5,6-diaminouracil2×

Product 1

HCID 1785242404-[1,3 bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acidYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The title compound was prepared from 1,3-bis(cyclohexylmethyl)-5,6-aminouracil by the method of J. Perutmattam, Syn. Commun. 1989, 19:3367-3370. 1,3-Bis(cyclohexylmethyl)-5,6-diaminouracil was freshly prepared by shaking a mixture of 6-amino-1,3-bis(cyclohexylmethyl)-5-nitrosouracil (from step (c) example 1, 2.00 g, 5.74 mmol) in methanol (250 mL)-water (25 mL) with 10% palladium on carbon (0.20 g) under hydrogen (40 psi) on a Parr shaker for 2 h. The catalyst was filtered off (Celite) and the colorless filtrate was concentrated to 50 mL. 4-Carboxybenzaldehyde (Aldrich, 860 mg, 5.73 mmol) was added to this solution of 1,3-bis(cyclohexylmethyl)-5,6-diaminouracil. The resulting yellow mixture was concentrated and the residual yellow solid dried by evaporation of several portions of absolute ethanol. The yellow powder (Schiff base) was then stirred in dimethoxyethane (80 mL) with iodine (1.6 g, 6.30 mequiv) at 60° C. (oil bath) for 24 h. A saturated aqueous solution of sodium thiosulfate (~15 mL) was added to the warm reaction mixture until complete decolorization of iodine resulted. The pale yellow precipitate was filtered off, washed with water, and dried at 0.5 Torr to give 4-[1,3 bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid as a pale yellow powder (2.13 g, 80%), m.p. >300° C.; 1 H-NMR (DMSO-d6) consistent with structure.

Workup

  1. filtrationThe catalyst was filtered off (Celite)
  2. concentrationthe colorless filtrate was concentrated to 50 mL
  3. concentrationThe resulting yellow mixture was concentrated
  4. dry with materialthe residual yellow solid dried by evaporation of several portions of absolute ethanol
  5. stirringThe yellow powder (Schiff base) was then stirred in dimethoxyethane (80 mL) with iodine (1.6 g, 6.30 mequiv) at 60° C. (oil bath) for 24 h
  6. additionA saturated aqueous solution of sodium thiosulfate (~15 mL) was added to the warm reaction mixture until complete decolorization of iodine
  7. customresulted
  8. filtrationThe pale yellow precipitate was filtered off
  9. washwashed with water
  10. customdried at 0.5 Torr

Sources & evidence

ORD record
ord-06c7ce2f0c444366bb51f94e42f6d5d7
Source dataset
uspto-grants-1998_07
Patent number
US05776940

Reaction notes

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