Piperidine → HCID 178423283, compound

HRID 1371163Notes

Reaction equation

HRID 1371163 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([C:9]([N:11]2[CH2:15][CH2:14]CC2)=[CH2:10])[CH:6]=[CH:7][CH:8]=1.CC(C1C=CC=C(C(F)(F)F)C=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:10][C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:16])[F:17])[CH:4]=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 676823'-(Trifluoromethyl)acetophenoneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511277HCID 18511277, compound

Product 1

HCID 178423283HCID 178423283, compoundYield 17%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(3-(trifluoromethyl)phenyl)vinyl]pyrrolidine (freshly prepared before use from 3-(trifluoromethyl)acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.97 g, 8.17 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.70 g, 8.17 mmol), N,N-diisopropylethylamine (1.4 mL, 8.17 mmol), piperidine (1.3 mL, 13.1 mmol), NEt3 (1.3 mL) and SnCl2 (25 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 500 mg (17%) of 2-methyl-4-piperidyl-6-[3-(trifluoromethyl)phenyl]pyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (500 mg, 1.39 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.40 mL, 1.40 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 493 mg (15%) of the title compound as a white colored solid. Mp: 241-243° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.72 (br s, 6), 2.59 (s, 3), 4.08 (s, 4), 7.14 (s, 1), 7.79 (t, 1, J=7.6), 7.85 (d, 1, J=7.5), 8.30 (d, 1, J=7.6), 8.34 (s, 1), 12.92 (s, 1), 14.53 (s, 1). MS m/z: 361 (M+1 for free base). Anal. Calcd for C19H19F3N4HCl.1.0H2O: C, 55.00; H, 5.35; N, 13.51; Cl, 8.55. Found: C, 54.99; H, 5.20; N, 13.39; 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-247ce078c25d4785a85d76e93f82845a
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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