Piperidine → HCID 178423304, compound

HRID 1371184Notes

Reaction equation

HRID 1371184 reaction equation
C1C2C(=C[C:6]([C:10]([N:12]3CCCC3)=[CH2:11])=CC=2)CC1.[C:17]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][CH2:24][CH2:23]2)(=O)[CH3:18].N1CC[CH2:31][CH2:30]1.[CH3:34][C:35]1[N:40]=[C:39](Cl)[C:38]([N+:42]([O-])=O)=[C:37](Cl)[N:36]=1.C(N(CC)C(C)C)(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH2:25]1[C:26]2[C:22](=[CH:21][C:20]([CH:17]3[NH:12][CH:10]([CH3:11])[CH2:6][CH:34]([C:35]4[NH:40][C:39]5=[CH:30][CH:31]=[N:42][C:38]5=[CH:37][N:36]=4)[CH2:18]3)=[CH:28][CH:27]=2)[CH2:23][CH2:24]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 2339761-(2,3-Dihydro-1H-inden-5-yl)ethan-1-oneHCID 18511392HCID 18511392, compound

Product 1

HCID 178423304HCID 178423304, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing (1-indan-5-ylvinyl)pyrrolidine (freshly prepared before use from 5-acetylindane (Avocado Chemical Company), pyrrolidine and TiCl4 (1.35 g, 6.34 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.35 g, 6.34 mmol), N,N-diisopropylethylamine (1.1 mL, 6.34 mmol), piperidine (1.0 mL, 10.1 mmol), NEt3 (1.1 mL) and SnCl2 (19 mL of a 2 M soln in DMF) In this example the 2 M SnCl2 solution was added to the reaction mixture at 140° C. Heating was then discontinued and the mixture was allowed to cool to room temperature. The mixture was stirred at room temperature for an additional 48 h. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 913 mg (43%) of 6-indan-5-yl-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This compound (909 mg, 2.75 mmol) was dissolved in 5:1 EtOAc/MeOH (50 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (2.80 mL, 2.80 mmol). The solution was allowed to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et3O (3×15 mL) and dried under vacuum at 60° C. to give 601 mg (26%) of the title compound as a beige colored solid. Mp: 164-167° C. 1H HMR (DMSO-d6; 500 MHz): δ 1.71 (br s, 6), 2.07 (quintet, 2, J=7.4), 2.56 (s, 3), 2.94 (quintet, 4, J=7.4), 4.05 (br S, 4), 6.83 (s, 1), 7.41 (d, 1, J=7.8), 7.72 (d, 1, J=8.0), 7.81 (s, 1), 11.88 (s, 1), 14.31 (s, 1). MS m/z: 333 (M+1 for free base). Anal. Calcd for C21H24N4.HCl.H2O: C, 65.18; H, 7.03; N, 14.48; Cl, 9.16. Found: C, 64.91; H, 6.96; N, 14.35; Cl, 9.22.

Workup

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

Sources & evidence

ORD record
ord-7defe0f8eee84bdb8c8154691c3b5ff5
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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