Piperidine → HCID 178423148, compound

HRID 1371177Notes

Reaction equation

HRID 1371177 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH2:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.F[C:23](F)(F)C1C=C(C(=O)C)C=C(C(F)(F)F)C=1.[NH:39]1CC[CH2:41][CH2:40]1.CC1[N:50]=[C:49](Cl)[C:48]([N+]([O-])=O)=[C:47](Cl)[N:46]=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:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C:13]2[N:15]=[C:16]([CH:17]3[CH2:41][CH2:40][NH:39][CH:19]([CH3:23])[CH2:18]3)[NH:50][C:49]3=[CH:48][CH:47]=[N:46][C:14]=23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 1216161-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-oneHCID 18511397HCID 18511397, compound

Product 1

HCID 178423148HCID 178423148, compound

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing [1-(3,5-bis(trifluoromethyl)phenyl)vinyl]pyrrolidine (freshly prepared before use from 3′,5′-bis(trifluoromethyl)acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.33 g, 4.30 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (0.90 g, 4.30 mmol), N,N-diisopropylethylamine (0.7 mL, 4.30 mmol), piperidine (0.7 mL, 6.90 mmol), NEt3 (1.0 mL) and SnCl2 (13 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica el with 95:5 CHCl3/MeOH as eluant to give 232 mg (13%) of 6-((3,5-bis(trifluoromethyl)phenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored oil. This material (232 mg, 0.54 mmol) was dissolved in 10:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.60 mL, 0.60 mmol). The solution was left to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 57 mg (3%) of the title compound as a beige colored solid. Mp: >280° C. 1H HMR (DMSO-d6; 500 MHz): δ 1.73 (br s, 6), 2.60 (s, 3), 4.10 (s, 4), 7.30 (s, 1), 8.22 (s, 1), 8.68 (s, 2), 12.27 (s, 1), 14.43 (s, 1). MS m/z: 429 (M+1 for free base). Anal. Calcd for C20H18F6N4.HCl: C, 51.68; H, 4.12; N, 12.05; Cl, 7.63. Found: C, 51.51; H, 4.17; N, 11.96; Cl, 7.82.

Workup

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

Sources & evidence

ORD record
ord-9df02c90f9ed4df3ba48ed6df0ee43bc
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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