Piperidine → HCID 178422580, compound

HRID 635706

Reaction equation

HRID 635706 reaction equation
C[C:2]1OC(C)=[CH:5][C:6]=1[N:7]1CC[CH2:9][CH2:8]1.[C:13]([C:16]1[CH:20]=[C:19]([CH3:21])[O:18][C:17]=1[CH3:22])(=O)[CH3:14].N1CCCC1.[CH3:28][C:29]1[N:34]=[C:33](Cl)[C:32]([N+:36]([O-])=O)=[C:31](Cl)[N:30]=1.C(N(CC)C(C)C)(C)C.N1CCCCC1.Cl[Sn]Cl.[OH-].[Na+]>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[CH3:22][C:17]1[O:18][C:19]([CH3:21])=[CH:20][C:16]=1[C:13]1[CH:14]=[C:31]2[NH:30][C:29]([CH:28]3[CH2:9][CH2:8][NH:7][CH:6]([CH3:5])[CH2:2]3)=[N:34][CH:33]=[C:32]2[N:36]=1

Participants

12

Reactant 8

HCID 8082PiperidineHCID 14798Sodium HydroxideHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 615273-Acetyl-2,5-dimethylfuranHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 124137142,5-Dimethyl-3-[1-pyrrolidinyl]furan

Product 1

HCID 178422580HCID 178422580, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing 2,5-dimethyl-3-[1-pyrrolidinyl]furan (freshly prepared before use from 3-acetyl-2,5-dimethylfuran (Aldrich Chemical Company), pyrrolidine and TiCl4 (4.88 g, 25.5 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (5.30 g, 25.5 mmol), N,N-diisopropyl ethylamine (4.5 mL, 25.5 mmol), piperidine (4.0 mL, 40.8 mmol), NEt3 (4.0 mL) and SnCl2 (77 mL of a 2 M soln in DMF). Note because of the increase in scale, the workup involved NaOH (15 g) and crushed ice (300 mL). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 1.01 g (13%) of 2,5-dimethyl-3-(2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl)furan as a beige colored powder. This material (1.01 g, 3.22 mmol) was dissolved in 2:1 EtOAc/MeOH (100 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (3.25 mL, 3.25 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 878 mg (10%) of the title compound as a white colored solid. Mp: 238-240° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.69 (br s, 6), 2.29 (s, 3), 2.44 (s, 3), 2.55 (s, 3), 4.01 (s, 4), 6.47 (s, 1), 6.55 (s, 1), 11.67 (s, 1), 14.18 (s, 1). MS m/z: 311 (M+1 for free base). Anal. Calcd for C18H22N4O.HCl.1.0H2O: C, 59.25; H, 6.91; N, 15.36; Cl, 9.72. Found: C, 59.19; H, 6.80; N, 15.30; Cl, 9.88.

Workup

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

Sources & evidence

ORD record
ord-a1531bc5dd7242b0b2af1bfb58dc8f49
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Linked notes

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