18-Crown-6 → N-cyclohexyl-4-[(2,6-dichloro-9H-purin-9-yl)methyl]-N-methylbenzamide

HRID 343341Notes

Reaction equation

HRID 343341 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.C1OCCOCCOCCOCCOCCOC1.[H-].[K+].Br[CH2:33][C:34]1[CH:49]=[CH:48][C:37]([C:38]([N:40]([CH3:47])[CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]2)=[O:39])=[CH:36][CH:35]=1>C(#N)C>[CH:41]1([N:40]([CH3:47])[C:38](=[O:39])[C:37]2[CH:48]=[CH:49][C:34]([CH2:33][N:8]3[CH:7]=[N:6][C:5]4[C:9]3=[N:10][C:2]([Cl:1])=[N:3][C:4]=4[Cl:11])=[CH:35][CH:36]=2)[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 82127Potassium hydrideHCID 53244122,6-DichloropurineHCID 14797401N-cyclohexyl-N-methyl-4-bromomethylbenzamide

Product 1

HCID 86753613N-cyclohexyl-4-[(2,6-dichloro-9H-purin-9-yl)methyl]-N-methylbenzamideYield 25.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 2,6-dichloropurine (500 mg, 2.64 minol) in acetonitrile (40 mL)at -10° C. was added 18-crown-6 (48 mg, 0.18 mmol) and potassium hydride (106 mg after ether wash of 35% dispersion in mineral oil, 2.64 mmol). The reaction was allowed to warm to room temperature and stirred for an additional 30 min. 4-Bromomethyl-N-methyl-N-cyclohexyl benzamide (900 mg, 2.90 mmol) was added in small amounts over 10 min and the mixture stirred under argon at 25° C. After 18 hr, the reaction was quenched by adding drops of acetic acid and the solvent removed under reduced pressure at <45° C. The residue was dissolved in ethyl acetate and washed with aqueous potassium carbonate, water and brine. The solvent was removed and the crude mixture (1.28 g) chromatographed (silica gel, CH2Cl2 /MeOH 100/7) to give pure 6A (278 mg, 25%). m.p. 134°-136° C. Anal calcd. for C20H21N5OCl2.0.25 H2O:C, 56.80; H, 5.08; N, 16.56; Cl, 16.80. Found: C, 57.00; H, 5.09; N, 16.20; Cl, 16.59.

Workup

  1. stirringthe mixture stirred under argon at 25° C
  2. waitAfter 18 hr
  3. customthe reaction was quenched
  4. additionby adding drops of acetic acid
  5. customthe solvent removed under reduced pressure at <45° C
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. washwashed with aqueous potassium carbonate, water and brine
  8. customThe solvent was removed
  9. customthe crude mixture (1.28 g) chromatographed (silica gel, CH2Cl2 /MeOH 100/7)

Sources & evidence

ORD record
ord-fac5ac72a1b3437bb1f4def6ace0a2a8
Source dataset
uspto-grants-1999_01
Patent number
US05861403

Reaction notes

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