Hydrochloric Acid → HCID 178430021, compound

HRID 1371191Notes

Reaction equation

HRID 1371191 reaction equation
FC1C=[C:4]([C:9]([N:12]2CCCC2)=[CH:10]C)C=C(F)C=1.[CH3:17][CH2:18][C:19]([C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=1)=[O:20].N1C[CH2:32][CH2:31][CH2:30]1.C[C:35]1[N:40]=[C:39]([Cl:41])[C:38]([N+:42]([O-])=O)=[C:37](Cl)[N:36]=1.C(N(CC)C(C)C)(C)C.N1CCCCC1.Cl[Sn]Cl.Cl>CN(C=O)C.CCOC(C)=O.CO.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[OH2:20].[ClH:41].[F:28][C:23]1[CH:22]=[C:21]([CH:19]2[NH:12][CH:9]([CH3:10])[CH2:4][CH:17]([C:35]3[NH:40][C:39]4=[C:31]([CH3:32])[CH:30]=[N:42][C:38]4=[CH:37][N:36]=3)[CH2:18]2)[CH:26]=[C:25]([F:27])[CH:24]=1

Participants

13

Reactant 8

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 1456203,5-DifluoropropiophenoneHCID 54177409HCID 54177409, compound

Product 1

HCID 178430021HCID 178430021, compoundYield 7%

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing (1-(3,5-difluorophenyl)prop-1-enyl) pyrrolidine (freshly prepared before use from 3,5-difluoropropiophenone (Lancaster Chemical Company), pyrrolidine and TiCl4 (2.29 g, 10.3 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.10 g, 10.3 mmol), N,N-diisopropylethylamine (1.8 mL, 10.3 mmol), piperidine (1.6 mL, 16.4 mmol), NEt3 (1.6 mL) and SnCl2 (31 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 give605 mg (17%) of 6-(3,5-difluorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored foam. This compound (600 mg, 1.75 mmol) was dissolved in 10:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.80 mL, 1.80 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 291 mg (7%) of the title compound as a beige colored solid. Mp: 242-245° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.52 (br s, 6), 2.28 (s, 3), 2.55 (s, 3), 3.97 (br s, 4), 7.36-7.41 (m, 3), 11.89 (s, 1), 13.82 (s, 1). MS m/z: 343 (M+1 for free base). Anal. Calcd for C19H20F2N4.HCl.0.5H2O: C, 58.83; H, 5.72; N, 14.45; Cl, 9.24. Found: C, 58.86; H, 5.72; N, 14.50; Cl, 9.29.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureto cool to room temperature
  3. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give605 mg (17%) of 6-(3,5-difluorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored foam
  4. temperatureheated to boiling
  5. temperatureto cool to room temperature
  6. filtrationThe resulting crystals were collected by filtration
  7. washwashed with EtOAc (2×10 mL), Et2O (3×15 mL)
  8. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-27f1ac8e112b46e387619eb748660d3b
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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