Trimethylsilyldiazomethane → 1-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-hydroxypiperidine-4-carboxylic Acid Methyl Ester

HRID 1246824Notes

Reaction equation

HRID 1246824 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[N:8]2[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:4][N:3]=1.[OH:25][C:26]1([C:32]([OH:34])=[O:33])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.[CH3:35][Si](C=[N+]=[N-])(C)C>CO.C1C=CC=CC=1>[CH3:35][O:33][C:32]([C:26]1([OH:25])[CH2:31][CH2:30][N:29]([C:4]2[N:3]=[CH:2][N:10]=[C:9]3[C:5]=2[N:6]=[C:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[Cl:24])[N:8]3[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH2:28][CH2:27]1)=[O:34]

Participants

5

Reactant 3

HCID 167693TrimethylsilyldiazomethaneHCID 44371984-hydroxypiperidine-4-carboxylic AcidHCID 21905840Chloro-9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purine

Product 1

HCID 587217061-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-hydroxypiperidine-4-carboxylic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 21927730Benzene methanolSolvent

Procedure

Chloro-9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purine I-(4A-7)c (59 mg, 0.16 mmol) and 4-hydroxy-piperidine-4-carboxylic acid (22 mg, 0.14 mmol) were coupled by the general method of Example 19. The crude product (ESI MS (M+1) 484) was dissolved in 1:1 methanol/benzene (0.6 ml) and then treated with trimethylsilyldiazomethane (2 M in hexanes, 0.17 ml, 0.34 mmol). After stirring for 1 hour the reaction was concentrated under a stream of nitrogen and then purified by preparative TLC using 4% methanol in methylene chloride to give title compound 23A-1 (31 mg, 44%). An ether/methylene chloride solution of the material was treated with excess 1 M HCl in ether, concentrated under a stream of nitrogen, and then triturated from ether to give the hydrochloride salt of compound 23A-1 (27 mg, 36% overall) as a light tan solid: +ESI MS (M+1) 498.1; 1H NMR (400 MHz, CD3OD) δ 8.38 (s, 1H), 7.62–7.59 (m, 1H), 7.51–7.40 (m, 5H), 7.34 (d, J=8.7 Hz, 2H), 3.90 (v br s, 2H), 3.75 (s, 3H), 2.25 (td, J=13.1, 4.1 Hz, 2H), 1.97 (br d, J=12.4 Hz, 2H).

Workup

  1. concentrationwas concentrated under a stream of nitrogen
  2. custompurified by preparative TLC

Sources & evidence

ORD record
ord-8e5c2937146846c3a83ec4e0d88d8833
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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