Piperidine → HCID 178421871, compound

HRID 1371183Notes

Reaction equation

HRID 1371183 reaction equation
[CH3:1][C:2]1[N:6](C2C=CC=CC=2)N=C[C:3]=1C(N1CCCC1)=C.[C:20]([C:23]1[CH:24]=[N:25][N:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:27]=1[CH3:28])(=O)[CH3:21].N1CC[CH2:37][CH2:36]1.[CH3:40][C:41]1[N:46]=[C:45](Cl)[C:44]([N+:48]([O-])=O)=[C:43](Cl)[N:42]=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>[CH3:1][CH:2]1[CH2:3][CH:40]([C:41]2[NH:46][C:45]3=[CH:36][CH:37]=[N:48][C:44]3=[CH:43][N:42]=2)[CH2:21][CH:20]([C:23]2[CH:24]=[N:25][N:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:27]=2[CH3:28])[NH:6]1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 802071-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)ethan-1-oneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 54519679HCID 54519679, compound

Product 1

HCID 178421871HCID 178421871, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Using the method described in Example 30 by employing 5-methyl-1-phenyl-4-(1-pyrrolidinylvinyl) pyrazole (freshly prepared before use from 4-acetyl-5-methyl-1-phenylpyrazole (Maybridge Chemical Company), pyrrolidine and TiCl4 (1.30 g, 5.14 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 5.14 mmol), N,N-diisopropylethylamine (1.0 mL, 5.14 mmol), piperidine (0.8 mL, 8.2 mmol), NEt3 (1.0 mL) and SnCl2 (15 mL of a 2 M soln in DMF). In this example the reaction mixture was stirred at room temperature for 48 h after the addition of 2 M SnCl2. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 701 mg (37%) of 2-methyl-6-(5-methyl-1-phenylpyrazol-4-yl)-4-piperidylpyrrolo[3,2-d]pyrimidine as a cream colored solid. This material (700 mg, 1.89 mmol) was dissolved in 4:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.90 mL, 1.90 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 637 mg (31%) of the title compound as white colored long needles. Mp: >280° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.48 (s, 3), 2.57 (s, 3), 4.04 (br s, 4), 6.57 (s, 1), 7.48-7.62 (m, 5), 8.16 (s, 1), 11.89 (s, 1), 14.13 (s, 1). MS m/z: 373 (M+1 for free base). Anal. Calcd for C22H24N6.HCl.0.25H2O: C, 63.86; H, 6.17; N, 20.32; Cl, 8.47. Found: C, 64.11; H, 6.18; N, 20.43; Cl, 8.57.

Workup

  1. customwas stirred at room temperature for 48 h
  2. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-067a0386c62f48798f6302fdfe84ce9b
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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