Formaldehyde → HCID 10160760, compound

HRID 2181622Notes

Reaction equation

HRID 2181622 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:14]([C:15]([NH:17][CH3:18])=[O:16])=[C:13]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])[N:12]=[C:11]1[CH2:28][CH3:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[CH3:32]C1C=CC(S(O)(=O)=O)=CC=1.O.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[C:15](=[O:16])[N:17]([CH3:32])[CH2:18][N:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[Cl:27])[C:13]=2[N:12]=[C:11]1[CH2:28][CH3:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 11154740HCID 11154740, compound

Product 1

HCID 10160760HCID 10160760, compoundYield 102.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 1-benzyloxymethyl-4-[(2,4-dichlorophenyl)amino]-2-ethyl-N-methyl-1H-imidazole-5-carboxamide (2.70 g, 6.23 mmol) dissolved in toluene (100 mL) was treated with paraformaldehyde (8.0 g) and p-TsOH.H2O (0.67 g, 3.52 mmol). The reaction mixture was heated at reflux for 15 min. The mixture was cooled to rt, and transferred to a separatory funnel containing saturated aqueous NaHCO3 (150 mL). The aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (40% ethyl acetate in hexanes) to afford 7-benzyloxymethyl-3-(2,4-dichlorophenyl)-8-ethyl-1-methyl-1,2,3,7-tetrahydro-6H-purin-6-one (1.6 g, 58% yield) as a colorless amorphous solid: 1H NMR (300 MHz, CDCl3) δ 7.46 (d, J=2.2 Hz, 1H), 7.34-7.29 (m, 5H), 7.19 (dd, J=8.4, 2.2 Hz, 1H), 7.03 (d, J=8.8 Hz, 1H), 5.84 (s, 2H), 4.85 (s, 2H), 4.71 (s, 2H), 2.97 (s, 3H), 2.77 (q, J=7.7 Hz, 2H), 1.28 (t, J=7.7 Hz, 3H); HRMS (ESI) m/e 445.1212 [(M+H)+, calcd for C22H23N4O2Cl2 445.1198].

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 15 min
  3. customtransferred to a separatory funnel
  4. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5c3b5e911cc8475aa7a698e893d19d44
Source dataset
uspto-grants-2005_05
Patent number
US06894045B2

Reaction notes

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