Piperidine → HCID 178423281, compound

HRID 635712Notes

Reaction equation

HRID 635712 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([N:11]1[CH2:15][CH2:14]CC1)=[CH2:10].FC(F)(F)CC(C1C=CC=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:10][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[C:2]([F:1])([F:16])[F:17])=[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 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 98341553,3,3-trifluoro-1-phenylpropan-1-oneHCID 18511169HCID 18511169, compound

Product 1

HCID 178423281HCID 178423281, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(2-(trifluoromethyl)phenyl)vinyl]pyrrolidine (freshly prepared before use from 2-(trifluoromethyl)acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.19 g, 4.94 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 4.94 mmol), N,N-diisopropylethylamine (0.9 mL, 4.94 mmol), piperidine (0.8 mL, 7.9 mmol), NEt3 (0.9 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 330 mg (19%) of 2-methyl-4-piperidyl-6-[2-(trifluoromethyl)phenyl]pyrrolo[3,2-d]pyrimidine as a tan colored solid. This material (330 mg, 0.90 mmol) was dissolved in 5:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.90 mL, 0.90 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 202 mg (11%) of the title compound as beige colored cube shaped crystals. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.70 (br s, 6), 2.58 (s, 3), 4.01 (s, 4), 6.62 (s, 1), 7.74 (d, 1, J=7.5), 7.79 (t, 1, J=7.5), 7.86 (t, 1, J=7.4), 7.97 (d, 1, J=7.8), 12.45 (s, 1), 14.43 (s, 1). MS m/z: 361 (H+1 for free base). Anal. Calcd for C19H19F3N4.HCl.H2O: C, 55.00; H, 5.35; N, 13.51; Cl, 8.55. Found: C, 55.25; H, 5.41; N, 13.31; Cl, 8.76.

Workup

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

Sources & evidence

ORD record
ord-1467b09f702b4eeabab54a4e9dae9b1e
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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