Piperidine → HCID 178423293, compound

HRID 1371178Notes

Reaction equation

[F:1][C:2]([F:18])([F:17])[S:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:16][CH2:15][CH2:14]C2)=C)=[CH:6][CH:5]=1.FC(F)(F)SC1C=CC(C(=O)C)=CC=1.N1CCCC1.[CH3:38][C:39]1[N:44]=C(Cl)C([N+]([O-])=O)=[C:41](Cl)[N:40]=1.C([N:53]([CH2:57][CH3:58])[CH:54]([CH3:56])[CH3:55])(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[F:18][C:2]([F:1])([F:17])[S:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:14]=[C:15]3[NH:44][C:39]([CH:38]4[CH2:58][CH2:57][NH:53][CH:54]([CH3:55])[CH2:56]4)=[N:40][CH:41]=[C:16]3[N:12]=2)=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 140 °C

Procedure

Using the method described in Example 30 by employing trifluoro[4-(1-pyrrolidinylvinyl)phenylthio]methane (freshly prepared before use from 4′-(trifluoromethylthio)acetophenone (Oakwood Products Inc.), pyrrolidine and TiCl4 (1.96 g, 7.17 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.50 g, 7.17 mmol), N,N-diisopropylethylamine (1.2 mL, 7.17 mmol), piperidine (1.1 mL, 11.5 mmol), NEt3 (1.1 mL) and SnCl2 (21 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 742 mg (26%) of trifluoro[4-(2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl)phenylthio]methane as a beige colored foam. This compound (741 mg, 1.90 mmol) was dissolved in 10:1 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.90 mL, 1.90 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 418 mg (13%) of the title compound as white colored needles. Mp: 270-272° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 4.00 (br s, 4), 6.96 (s, 1), 7.84 (d, 2, J=8.1), 8.06 (d, 2, J=8.2), 12.12 (s, 1), 14.39 (s, 1). MS m/z: 393 (M+1 for free base). Anal. Calcd for C19H19F3N4S.HCl.H2O: C, 51.06; H, 4.96; N, 12.54; Cl, 7.93. Found: C, 51.02; H, 4.98; N, 12.46; Cl, 8.02.

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-8bb477fe2de941ab879c8f1a55b7f991
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06583154B1

Reaction notes

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