Piperidine → HCID 178423329, compound

HRID 1371203Notes

Reaction equation

HRID 1371203 reaction equation
ClC1C=CC([C:8]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:9]F)=CC=1.Cl[C:17]1[CH:22]=[CH:21][C:20]([C:23](=O)[CH2:24]F)=[CH:19][CH:18]=1.N1CCCC1.[CH3:32][C:33]1[N:38]=[C:37](Cl)[C:36]([N+:40]([O-])=O)=[C:35](Cl)[N:34]=1.[CH:44]([N:47](CC)C(C)C)([CH3:46])[CH3:45].N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:45][CH:44]1[CH2:46][CH:32]([C:33]2[NH:38][C:37]3=[C:8]([N:11]4[CH2:12][CH2:13][CH2:14][CH2:15]4)[CH:9]=[N:40][C:36]3=[CH:35][N:34]=2)[CH2:24][CH:23]([C:20]2[CH:21]=[CH:22][CH:17]=[CH:18][CH:19]=2)[NH:47]1

Participants

11

Reactant 7

HCID 8082Piperidine2×HCID 24479Stannous Chloride3×HCID 31268Pyrrolidine2×HCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 3198991-(4-chlorophenyl)-2-fluoroethanoneHCID 54560181HCID 54560181, compound

Product 1

HCID 178423329HCID 178423329, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing (1-(4-chlorophenyl)-2-fluorovinyl]pyrrolidine (freshly prepared before use from 1-(4-chlorophenyl)-2-fluoroethan-1-one (Example 153(a)), pyrrolidine and TiCl4 (see Example 30) (3.00 g, 13.3 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.80 g, 13.3 mmol), N,N-diisopropylethylamine (2.3 mL, 13.3 mmol), piperidine (2.1 mL, 21.3 mmol), NEt3 (2.2 mL) and SnCl2 (40 mL of a 2 M soln in DMF). In this example, the SnCl2 solution was added to the reaction mixture at 140° C. (Note: When both the piperidine displacement and the SnCl2 reduction sequences are performed at 140° C. the pyrrolidine moiety is incorporated). The mixture was stirred at 140° C. for an additional 16 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The residue was purified by flash chromatography on silica gel with 50:50 EtOAc/hexanes as eluant to give 0.38 g (8%) of 2-methyl-6-phenyl-4-piperidyl-7-pyrrolidinylpyrrolo[3,2-d]pyrimidine as a brown colored solid. This compound (0.38 g, 1.00 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.00 mL, 1.00 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×5 mL), Et2O (3×5 mL) and dried under vacuum at 60° C. to give 162 mg (2%) of the title compound as a beige colored powder. Mp: >280° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.49 (br s, 2), 1.54 (br s, 4), 1.88 (br s, 2), 2.01 (br s, 2), 2.59 (s, 3), 2.92 (br s, 4), 3.72 (br s, 2), 4.04 (br s, 2), 7.57 (d, 2, J=8.5), 7.76 (d, 2, J=8.4), 11.44 (s, 1), 13.13 (s, 1). MS m/z: 396 (M+1 for free base). Anal. Calcd for C22H26ClN4.HCl.0.5H2O: C, 59.86; H, 6.39; N, 15.87; Cl, 16.06. Found: C, 59.56; H, 6.36; N, 15.70; Cl, 15.95.

Workup

  1. customwas added to the reaction mixture at 140° C.
  2. customare performed at 140° C.
  3. temperatureto cool to room temperature
  4. customThe residue was purified by flash chromatography on silica gel with 50:50 EtOAc/hexanes as eluant

Sources & evidence

ORD record
ord-a5e40474036a448da26a12f1341b9832
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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