Piperidine → HCID 178430019, compound

HRID 635753Notes

Reaction equation

FC1C=[C:4]([C:9]([N:12]2CCCC2)=[CH:10]C)C=CC=1F.[CH3:17][CH2:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[C:23]([F:28])[CH:22]=1)=O.N1C[CH2:32][CH2:31][CH2:30]1.C[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>[F:28][C:23]1[CH:22]=[C:21]([CH:19]2[NH:12][CH:9]([CH3:10])[CH2:4][CH:17]([C:35]3[NH:40][C:39]4=[C:31]([CH3:32])[CH:30]=[N:42][C:38]4=[CH:37][N:36]=3)[CH2:18]2)[CH:26]=[CH:25][C:24]=1[F:27]

Participants

Conditions

Temperature: 140 °C

Procedure

Using the method described in Example 30 by employing [1-(3,4-difluorophenyl)prop-1-enyl]pyrrolidine (freshly prepared before use from 3,4-difluoropropiophenone (Lancaster Chemical Company), pyrrolidine and TiCl4 (2.27 g, 10.2 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.11 g, 10.2 mmol), N,N-diisopropylethylamine (1.8 mL, 10.2 mmol), piperidine (1.6 mL, 16.3 mmol), NEt3 (2.3 mL) and SnCl2 (31 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 305 mg (9%) of 6-(3,4-difluorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored oil. This compound (304 mg, 0.89 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.90 mL, 0.90 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 201 mg (5%) of the title compound as a beige colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.63 (br s, 6), 2.27 (s, 3), 2.56 (s, 3), 3.98 (br s, 4), 7.47-7.49 (m, 1), 7.61 (q, 1, J=8.6), 7.78 (dt, 1, J=1.4, 7.8), 11.96 (s, 1), 14.08 (s, 1). MS m/z: 343 (M+1 for free base). Anal. Calcd for C19H20F2N4.1.1HCl: C, 59.64; H, 5.56; N, 14.65; Cl, 10.22. Found: C, 59.59; H, 5.56; N, 14.67; Cl, 10.02.

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-4aece697540b4435945baaab1cd6f026
Source dataset: uspto-grants-2001_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06187777B1

Reaction notes

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