Piperidine → HCID 178423566, compound

HRID 1371211Notes

Reaction equation

HRID 1371211 reaction equation
[CH3:1][C:2]1[C:3]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:13][CH2:12][CH2:11]C1)=C.N1CCCC1.[CH3:24][C:25]1[N:30]=C(Cl)C([N+]([O-])=O)=[C:27](Cl)[N:26]=1.C([N:39]([CH2:43][CH3:44])[CH:40]([CH3:42])[CH3:41])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:1][C:2]1[C:3]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:4]=2[S:5][C:6]=1[C:7]1[CH:11]=[C:12]2[NH:30][C:25]([CH:24]3[CH2:44][CH2:43][NH:39][CH:40]([CH3:41])[CH2:42]3)=[N:26][CH:27]=[C:13]2[N:9]=1

Participants

10

Reactant 6

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511264HCID 18511264, compound

Product 1

HCID 178423566HCID 178423566, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 3,5-dimethyl-2-(1-pyrrolidinylvinyl)benzo[b]thiophene (freshly prepared before use from 2-acetyl-3,5-dimethyl[b]thiophene (Avocado Chemical Company), pyrrolidine and TiCl4 (1.81 g, 7.04 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.46 g, 7.04 mmol), N,N-diisopropylethylamine (1.2 mL, 7.04 mmol), piperidine (1.1 mL, 11.3 mmol), NEt3 (1.5 mL) and SnCl2 (21 mL of a 2 M soln in DMF). In this example the SnCl2 solution was added to the reaction mixture at 140° C. 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 95:5 CHCl3/MeOH as eluant to give 0.53 g (20%) of 3,5-dimethyl-2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzo[b]thiophene as a cream colored solid. This compound (530 mg, 1.41 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.50 mL, 1.50 mmol). The solution was allowed 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 493 mg (17%) of the title compound as a yellow colored solid. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 6 1.64 (br s, 6), 2.43 (s., 3), 2.44 (s, 3), 2.51 (s, 3), 3.98 (br s, 4), 6.65 (s, 1), 7.27 (d, 1, J=8.2), 7.66 (s, 1), 7.87 (d, 1, J=8.3), 12.31 (s, 1), 14.13 (s, 1). MS m/z: 377 (M+1 for free base). Anal. Calcd for C22H24N4S.HCl.H2O: C, 61.31; H, 6.31; N, 13.00; Cl, 8.23. Found: C, 61.26; H, 5.92; N, 12.91; Cl, 8.32.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureto cool to room temperature
  3. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-cbb601a0af194a8b8e4c316d3d54a566
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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