Piperidine → HCID 178423280, compound

HRID 1371198Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][C:12]([C:14]([N:16]3[CH2:20][CH2:19][CH2:18]C3)=C)=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].ClC1C=C(C2OC(C(=O)C)=CC=2)C=CC=1F.N1CCCC1.[CH3:42][C:43]1[N:48]=C(Cl)C([N+]([O-])=O)=[C:45](Cl)[N:44]=1.C([N:57]([CH2:61][CH3:62])[CH:58]([CH3:60])[CH3:59])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][C:12]([C:14]3[CH:18]=[C:19]4[NH:48][C:43]([CH:42]5[CH2:62][CH2:61][NH:57][CH:58]([CH3:59])[CH2:60]5)=[N:44][CH:45]=[C:20]4[N:16]=3)=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 140 °C

Procedure

Using the method described in Example 30 by employing 5-(3-chloro-4-fluorophenyl)-2-(1-pyrrolidinylvinyl)furan (freshly prepared before use from 1-[5-(3-chloro-4-fluorophenyl)-2-furyl]ethan-1-one (Maybridge Chemical Company), pyrrolidine and TiCl4 (1.65 g, 5.67 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.20 g, 5.67 mmol), N,N-diisopropylethylamine (1.0 mL, 5.67 mmol), piperidine (0.9 mL, 9.1 mmol), NEt3 (1.0 mL) and SnCl2 (17 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 0.61 g (26%) of 5-(3-chloro-4-fluorophenyl)-2-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]furan as a beige colored solid. This compound (609 mg, 1.50 mmol) was dissolved in 10:1 EtOAc/MeOH (25 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 385 mg (15%) of the title compound as tan colored small needles. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 4.00 (br s, 4), 6.89 (s, 1), 7.26 (d, 1, J=3.7), 7.47 (d, 1, J=3.7), 7.50 (t, 1, J=9.0), 7.85-7.89 (m, 1), 8.10 (dd, 1, J=2.1, 7.1), 12.19 (s, 1), 14.31 (s, 1). MS m/z: 411 (M+1 for free base). Anal. Calcd for C22H20ClFN4O.HCl.1.5H2O: C, 55.70; H, 5.10; N. 11.81; Cl, 14.95. Found: C, 55.80; H, 5.10; N, 11.72; Cl, 15.06.

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-72ebe1e49bff4d95949e12310f3195c0
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06583154B1

Reaction notes

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