Piperidine → HCID 178423284, compound

HRID 1371167Notes

Reaction equation

HRID 1371167 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13]C2)=C)=[CH:5][CH:4]=1.CC(C1C=CC(C(F)(F)F)=CC=1)=O.N1CCCC1.[CH3:36][C:37]1[N:42]=C(Cl)C([N+]([O-])=O)=[C:39](Cl)[N:38]=1.C([N:51]([CH2:55][CH3:56])[CH:52]([CH3:54])[CH3:53])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:54][CH:52]1[CH2:53][CH:36]([C:37]2[NH:42][C:14]3=[CH:13][C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:8][CH:7]=4)=[N:11][C:15]3=[CH:39][N:38]=2)[CH2:56][CH2:55][NH:51]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 697311-(4-(Trifluoromethyl)phenyl)ethan-1-oneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 22719888HCID 22719888, compound

Product 1

HCID 178423284HCID 178423284, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-[4-(trifluoromethyl)phenyl]vinyl]pyrrolidine (freshly prepared before use from 4-(trifluoromethyl) acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.21 g, 5.02 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 5.02 mmol), N,N-diisopropylethylamine (0.9 mL, 5.02 mmol), piperidine (0.8 mL, 8.0 mmol), NEt3 (1.0 mL) and SnCl2 (15 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 248 mg (14%) of 2-methyl-4-piperidyl-6-[4-(trifluoromethyl)phenyl]pyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (245 mg, 0.69 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.70 mL, 0.70 mmol). The solution was left 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 187 mg (10%) of the title compound as a beige colored solid. Mp: 278-280° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.72 (br s, 6), 2.58 (s, 3), 4.08 (s, 4), 7.05 (s, 1), 7.93 (d, 2, J=8.3), 8.20 (d, 2, J=8.2), 12.16 (s, 1), 14.32 (s, 1). MS m/z: 361 (M+1 for free base). Anal. Calcd for C19H19F3N4.HCl.1.5H2O: C, 53.79; H, 5.43; N, 13.21; Cl, 8.26. Found: C, 54.01; H, 5.40; N, 13.18; Cl, 8.60.

Workup

  1. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-4a76bf0bda974523981dd19c4b3ecb85
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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