Triethylamine → 1-[9-(4-Chloro-phenyl)-8-(2,4-dichloro-phenyl)-9H-purin-6-yl]-piperidine-4-carboxylic acid Ethyl Ester

HRID 1246812Notes

Reaction equation

HRID 1246812 reaction equation
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[Cl:25])[N:6]2[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1.[CH2:26]([O:28][C:29]([CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30])[CH3:27].C(N(CC)CC)C>C(O)C>[CH2:26]([O:28][C:29]([CH:31]1[CH2:36][CH2:35][N:34]([C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[C:5]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[N:6]3[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH2:33][CH2:32]1)=[O:30])[CH3:27]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 70770Ethyl 4-piperidinecarboxylateHCID 219058016-chloro-9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-9H-purine

Product 1

HCID 587217041-[9-(4-Chloro-phenyl)-8-(2,4-dichloro-phenyl)-9H-purin-6-yl]-piperidine-4-carboxylic acid Ethyl Ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

6-chloro-9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-9H-purine I-(1A-1)d (30 mg, 0.07 mmol), piperidine-4-carboxylic acid ethyl ester (34 mg, 0.22 mmol), and triethylamine (20 μl, 0.29 mmol) were combined in ethanol (1 ml) and heated at 70° C. for 2 hours. The reaction mixture was concentrated under a stream of N2 and then extracted into ethyl acetate from saturated NaHCO3 solution. The organic layers were combined, dried (Na2SO4), filtered, evaporated to dryness, and then purified by preparative TLC using 4% methanol in methylene chloride as eluant to obtain title compound 7A-1. A solution of the material in methylene chloride was treated with excess 1 N HCl in diethyl ether, stirred and evaporated to dryness to afford the hydrochloride salt of compound 7A-1 (24 mg, 65%) as a solid: +ESI MS (M+1) 530.1; 1H NMR (400 MHz, CD3OD) δ 8.35 (s, 2H), 7.60 (d, J=8.3 Hz, 1H), 7.56 (d, J=2.1 Hz, 1H), 7.50–7.45 (m, 3H), 7.34 (d, J=8.7 Hz, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.68 (v br s, 2H), 2.85 (m, 1H), 2.16 (m, 2H), 1.89 (m, 2H), 1.25 (t, J=7.1 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under a stream of N2
  2. extractionextracted into ethyl acetate from saturated NaHCO3 solution
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated to dryness
  6. custompurified by preparative TLC

Sources & evidence

ORD record
ord-878c6b6124af468493f6b976cc9ea0d0
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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