Piperidine → HCID 178421818, compound

HRID 635744Notes

Reaction equation

HRID 635744 reaction equation
[CH3:1][C:2]1[C:3]2[CH:17]=[CH:16][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.[CH3:23][C:24]1[N:29]=C(Cl)C([N+]([O-])=O)=[C:26](Cl)[N:25]=1.C([N:38]([CH2:42][CH3:43])[CH:39]([CH3:41])[CH3:40])(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]=[CH:16][CH:15]=[CH:14][C:4]=2[S:5][C:6]=1[C:7]1[CH:11]=[C:12]2[NH:29][C:24]([CH:23]3[CH2:43][CH2:42][NH:38][CH:39]([CH3:40])[CH2:41]3)=[N:25][CH:26]=[C:13]2[N:9]=1

Participants

10

Reactant 6

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511282HCID 18511282, compound

Product 1

HCID 178421818HCID 178421818, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing 3-methyl-2-(1-pyrrolidinylvinyl)benzo[b]thiophene (freshly prepared before use from 2-acetyl-3-methylthianaphthene (Avocado Chemical Company), pyrrolidine and TiCl4 (1.67 g, 6.88 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.43 g, 6.88 mmol), N,N-diisopropylethylamine (1.2 mL, 6.88 mmol), piperidine (1.1 mL, 11.0 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 0.60 g (24%) of 3-methyl-2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzo[b]thiophene as a beige colored solid. This compound (596 mg, 1.64 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.70 mL, 1.70 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 421 mg (16%) of the title compound as a pale yellow colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.46 (s, 3), 2.51 (s, 3), 3.98 (br s, 4), 6.67 (s, 1), 7.41-7.47 (m, 2), 7.87 (dd, 1, J=1.7, 6.2), 7.99 (dd, 1, J=1.7, 6.4), 12.43 (s, 1), 14.38 (s, 1). MS m/z: 363 (M+1 for free base). Anal. Calcd for C21H22N4S.HCl.0.4H2O: C, 62.10; H, 5.91; N, 13.80; Cl, 8.73. Found: C, 62.04; H, 5.92; N, 13.80; Cl, 8.83.

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-4cb28389768543b08ba64152e393db11
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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