Piperidine → HCID 178422581, compound

HRID 1371162Notes

Reaction equation

HRID 1371162 reaction equation
[CH3:1][C:2]1[S:3][C:4]([CH3:14])=[CH:5][C:6]=1[C:7]([N:9]1[CH2:13][CH2:12][CH2:11]C1)=C.C(C1C=C(C)SC=1C)(=O)C.N1CCCC1.[CH3:30][C:31]1[N:36]=C(Cl)C([N+]([O-])=O)=[C:33](Cl)[N:32]=1.C([N:45]([CH2:49][CH3:50])[CH:46]([CH3:48])[CH3:47])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:1][C:2]1[S:3][C:4]([CH3:14])=[CH:5][C:6]=1[C:7]1[CH:11]=[C:12]2[NH:36][C:31]([CH:30]3[CH2:50][CH2:49][NH:45][CH:46]([CH3:47])[CH2:48]3)=[N:32][CH:33]=[C:13]2[N:9]=1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 5201913-Acetyl-2,5-dimethylthiopheneHCID 18511279HCID 18511279, compound

Product 1

HCID 178422581HCID 178422581, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing 2,5-dimethyl-3-(1-pyrrolidinylvinyl)thiophene (freshly prepared from 3-acetyl-2,5-dimethylthiophene (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.40 g, 6.76 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.40 g, 6.76 mmol), N,N-diisopropyl ethylamine (1.2 mL, 6.76 mmol), piperidine (1.1 mL, 10.8 mmol), NEt3 (1.2 mL) and SnCl2 (20 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 335 mg (15%) of 2,5-dimethyl-3-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]thiophene as a tan colored solid. This material (335 mg, 1.00 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.00 mL, 1.00 mmol). The solution was left to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 222 mg (9%) of the title compound as a beige colored solid. Mp: 240-241.5° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.70 (br s, 6), 2.44 (s, 3), 2.50 (s, 3), 2.55 (s, 3), 4.02 (br s, 4), 6.54 (s, 1), 7.06 (s, 1), 11.89 (s, 1), 14.15 (s, 1). MS m/z: 327 (M+1 for free base). Anal. Calcd for C18H22N4S.HCl.1.5H2O: C, 55.53; H, 6.68; N, 14.40; Cl, 9.00; S, 8.23. Found: C, 55.62; H, 6.66; N, 14.31; Cl, 9.13; S, 8.28.

Workup

  1. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-82bb88d3fd31470bb08d103bfb194df0
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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