Piperidine → HCID 178487381, compound

HRID 1371196Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13]C2)=C)[CH:6]=[C:5]([O:16][CH3:17])[C:4]=1[O:18][CH3:19].CC(C1C=C(OC)C(OC)=C(OC)C=1)=O.N1CCCC1.[CH3:40][C:41]1[N:46]=C(Cl)C([N+]([O-])=O)=[C:43](Cl)[N:42]=1.C([N:55]([CH2:59][CH3:60])[CH:56]([CH3:58])[CH3:57])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:17][O:16][C:5]1[CH:6]=[C:7]([C:9]2[CH:13]=[C:14]3[NH:46][C:41]([CH:40]4[CH2:60][CH2:59][NH:55][CH:56]([CH3:57])[CH2:58]4)=[N:42][CH:43]=[C:15]3[N:11]=2)[CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[O:18][CH3:19]

Participants

Conditions

Temperature: 140 °C

Procedure

Using the method described in Example 30 by employing 1,2,3-trimethoxy-5-(1-pyrrolidinylvinyl) benzene (freshly prepared before use from 3,4,5-trimethoxyacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.70 g, 6.46 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.35 g, 6.46 mmol), N,N-diisopropylethylamine (1.1 mL, 6.46 mmol), piperidine (1.0 mL, 10.3 mmol), NEt3 (1.1 mL) and SnCl2 (19 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 0.85 g (35%) of 1,2,3-trimethoxy-5-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene as a beige colored solid. This compound (466 mg, 1.20 mmol) was dissolved in 1:3 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.20 mL, 1.20 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 409 mg (29%) of the title compound as white colored crystals. Mp: 275-277° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.52 (s, 3), 3.66 (s, 3), 3.39 (s, 6), 3.99 (br t, 4, J=5.2), 6.85 (s, 1), 7.75 (s, 2), 11.94 (s, 1), 14.28 (s, 1). MS m/z: 381 (M+1 for free base). Anal. Calcd for C21H26N4O3.HCl: C, 60.21; H, 6.50; N, 13.37; Cl, 8.46. Found: C, 60.24; H, 6.53; N, 13.37; Cl, 8.57.

Workup

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

Sources & evidence

ORD record: ord-32f8a7ceb3754e93951092d769d7fe2e
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06583154B1

Reaction notes

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