Piperidine → HCID 178422580, 화합물

HRID 1371164

반응식

HRID 1371164 반응식
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

참가 물질

12

반응물 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

생성물 1

HCID 178422580HCID 178422580, 화합물수율 13%

시약·촉매·용매 3

HCID 24193Titanium Tetrachloride촉매HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

실험 절차

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 HMR (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.

후처리

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

출처 및 근거

ORD 기록
ord-70a2ba5b610745d9b407d80c40e6a606
출처 데이터셋
uspto-grants-2003_06
특허 번호
US06583154B1

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