Hydrochloric Acid → HCID 19104981, compound

HRID 1197789Notes

Reaction equation

HRID 1197789 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[C:9]2=[O:24])=[CH:4][CH:3]=1.[H-].[Na+].[CH:27]1[CH:32]=[C:31](CBr)[CH:30]=[C:29]([C:35]#[N:36])[CH:28]=1.N[C@H](C([Cl:48])=O)CC1C=CC=CC=1.N[C@H](C(C#N)=O)CC1C=CC=CC=1.Cl>C1COCC1>[ClH:1].[ClH:48].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[C:10]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:35]#[N:36])[CH:28]=3)([CH2:17][C:18]3[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=3)[C:9]2=[O:24])=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 13816782HCID 13816782, compoundHCID 19104983HCID 19104983, compoundHCID 54561241HCID 54561241, compound

Product 1

HCID 19104981HCID 19104981, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The solution of 1,3-dihydro-1-(4-chlorophenyl)-3-(4-pyridinylmethyl)-2H-pyrrolo[2,3-b]pyridin-2-one (3.0 g, 8.93 mmol) in 75 ml dry THF was treated with NaH (0.26 g, 10.7 mmol) and stirred at room temperature for min. The mixture was then treated dropwise with a solution of a-bromo-m-tolunitrile (1.93 g, 9.82 mmol) dissolved in 25 ml dry THF. The mixture was stirred at room temperature under dry nitrogen for 24 h and concentrated in vacuo. The residue was partitioned between 150 ml CH2Cl2 and 100 ml water. The organic layer was washed with additional water then brine, dried over anh. MgSO4, filtered, and concentrated to a foam. The foam was dissolved in a minimum amount of MeOH and chromatographed on silica gel using CHCl3 --MeOH (95:5) as mobile phase. The appropriate fractions were combined, concentrated in vacuo to 25 ml, and treated with 1N HCl--Et2O (10 ml). The resulting gummy mixture was concentrated to a foam which was triturated with Et2O, collected by filtration, washed with additional Et2O, and dried to give the desire product in 87% (3.8 g) yield as a foam; IR(nujol): 2229 (CN), 1723 (CO) cm-1 ; 1H NMR(DMSOd6TMS): d 3.4-3.6(dd, 2H, CH2 -Phe), 3.6-3.85 (dd, 2H, CH2 -Pyr), [6.91 (d, 2H), 7.25 (m, 3H), 7.61 (m, 3H), Phe-Cl and Phe-CN], [7.37 (dd, 1H), 7.96 (d, 1H), 8.20 (d, 1H), 2,3-Pyr], [7.51 (d, 2H), 8.71 (d, 2H), 1,4-Pyr]; mass spec m/e 451 (M+1). Anal calcd for C27H19N4OCl HCl, MW 487.39: C, 66.54; H, 4.14; N, 11.50. Found:

Workup

  1. stirringThe mixture was stirred at room temperature under dry nitrogen for 24 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between 150 ml CH2Cl2 and 100 ml water
  4. washThe organic layer was washed with additional water
  5. dry with materialbrine, dried over anh. MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to a foam
  8. dissolutionThe foam was dissolved in a minimum amount of MeOH
  9. customchromatographed on silica gel
  10. concentrationconcentrated in vacuo to 25 ml
  11. additiontreated with 1N HCl--Et2O (10 ml)
  12. concentrationThe resulting gummy mixture was concentrated to a foam which
  13. customwas triturated with Et2O
  14. filtrationcollected by filtration
  15. washwashed with additional Et2O
  16. customdried
  17. customto give the desire product in 87% (3.8 g)
  18. customyield as a foam

Sources & evidence

ORD record
ord-bfcf85810dd24df787c221f298299356
Source dataset
uspto-grants-1994_01
Patent number
US05278162

Reaction notes

Loading…