Diisopropylethylamine → 6-((4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)-1-methyl-4-(3-((trimethylsilyl)ethynyl)phenyl)-1,8-naphthyridin-2(1H)-one

HRID 1799168Notes

Reaction equation

HRID 1799168 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.CCN(C(C)C)C(C)C.C([Mg]Cl)(C)C.[Cl:22][C:23]1[CH:54]=[CH:53][C:26]([C:27]([C:29]2[CH:30]=[C:31]3[C:36](=[N:37][CH:38]=2)[N:35]([CH3:39])[C:34](=[O:40])[CH:33]=[C:32]3[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[C:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[CH:42]=2)=[O:28])=[CH:25][CH:24]=1>C(Cl)Cl>[Cl:22][C:23]1[CH:54]=[CH:53][C:26]([C:27]([OH:28])([C:2]2[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=2)[C:29]2[CH:30]=[C:31]3[C:36](=[N:37][CH:38]=2)[N:35]([CH3:39])[C:34](=[O:40])[CH:33]=[C:32]3[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[C:48][Si:49]([CH3:50])([CH3:52])[CH3:51])[CH:42]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 674288306-(4-chlorobenzoyl)-1-methyl-4-(3-((trimethylsilyl)ethynyl)phenyl)-1,8-naphthyridin-2(1H)-oneHCID 178418918HCID 178418918, compound

Product 1

HCID 593347576-((4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)-1-methyl-4-(3-((trimethylsilyl)ethynyl)phenyl)-1,8-naphthyridin-2(1H)-oneYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-bromo-1-methylimidazole (0.68 g, 4.26 mmol) in dry DCM (15 mL), DIPEA (0.77 mL, 4.47 mmol) and iPrMgCl (2.13 mL, 4.26 mmol, 2.0 M solution in THF) was added at 10° C. The reaction mixture was stirred for 1.5 h and a solution of compound J (0.5 g, 1.06 mmol) in DCM was added to it. The reaction mixture was refluxed for 2 h and quenched with saturated NH4Cl solution. The product was extracted with DCM (30 mL). The organic layer was dried, filtered and concentrated to give crude c. Purification of the crude product provided 210 mg (36%) of compound K.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 h
  2. customquenched with saturated NH4Cl solution
  3. extractionThe product was extracted with DCM (30 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude c
  8. customPurification of the crude product

Sources & evidence

ORD record
ord-e6a68075a5ae407c8c14952fed5ff5dd
Source dataset
uspto-grants-2013_01
Patent number
US08343996B2

Reaction notes

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