Piperidine → HCID 178488454, compound

HRID 635752Notes

Reaction equation

[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]([C:12]([N:14]3[CH2:18][CH2:17][CH2:16]C3)=C)=[CH:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.C(C1OC2C(OC)=CC=CC=2C=1)(=O)C.N1CCCC1.[CH3:38][C:39]1[N:44]=C(Cl)C([N+]([O-])=O)=[C:41](Cl)[N:40]=1.C([N:53]([CH2:57][CH3:58])[CH:54]([CH3:56])[CH3:55])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]([C:12]3[CH:16]=[C:17]4[NH:44][C:39]([CH:38]5[CH2:58][CH2:57][NH:53][CH:54]([CH3:55])[CH2:56]5)=[N:40][CH:41]=[C:18]4[N:14]=3)=[CH:11][C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 140 °C

Procedure

Using the method described in Example 30 by employing 7-methoxy-2-(1-pyrrolidinylvinyl)benzo[b]furan (freshly prepared before use from 2-acetyl-7-methoxybenzo[b]furan (Avocado Chemical Company), pyrrolidine and TiCl4 (1.89 g, 7.77 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.61 g, 7.77 mmol), N,N-diisopropylethylamine (1.4 mL, 7.77 mmol), piperidine (1.2 mL, 12.4 mmol), NEt3 (1.7 mL) and SnCl2 (23 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 0.27 g (10%) of 7-methoxy-2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzo[b]furan as a brown colored powder. This compound (0.26 g, 0.72 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.80 mL, 0.80 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 195 mg (7%) of the title compound as a yellow colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.66 (br s, 6), 2.51 (s, 3), 3.92 (s, 3), 4.01 (br s, 4), 6.88 (s, 1), 6.98 (d, 1, J=9.6), 7.20 (t, 1, J=7.8), 7.28 (d, 1, J=7.7), 7.72 (s, 1), 12.31 (s, 1), 14.09 (s, 1). MS m/z: 363 (M+1 for free base). Anal. Calcd for C21H22N4O2.HCl.0.3H2O: C, 62.38; H, 5.88; N, 13.86; Cl, 8.77. Found: C, 62.31; H, 5.81; N, 13.60; Cl, 8.82.

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-a21580d451964d69a8ef278871dd59d3
Source dataset: uspto-grants-2001_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06187777B1

Reaction notes

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