Sodium hydride → 2-(4-Chloro-phenyl)-5-[3-methoxy-4-(3-methyl-3H-imidazol-4-ylmethoxy)-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one

HRID 601535Notes

Reaction equation

HRID 601535 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[CH:5][N:4]=[CH:3]1.C(Cl)(=O)C(Cl)=O.[H-].[Na+].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[S:25][C:26]3[C:27](=[O:42])[N:28]([C:33]4[CH:38]=[CH:37][C:36](O)=[C:35]([O:40][CH3:41])[CH:34]=4)[CH:29]=[CH:30][C:31]=3[N:32]=2)=[CH:20][CH:19]=1>C(Cl)Cl.CN(C=O)C.O>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[S:25][C:26]3[C:27](=[O:42])[N:28]([C:33]4[CH:38]=[CH:37][C:36]([O:8][CH2:7][C:6]5[N:2]([CH3:1])[CH:3]=[N:4][CH:5]=5)=[C:35]([O:40][CH3:41])[CH:34]=4)[CH2:29][CH2:30][C:31]=3[N:32]=2)=[CH:20][CH:19]=1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 2773450(1-methyl-1H-imidazol-5-yl)methanolHCID 575017652-(4-Chloro-phenyl)-5-(4-hydroxy-3-methoxy-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 575017672-(4-Chloro-phenyl)-5-[3-methoxy-4-(3-methyl-3H-imidazol-4-ylmethoxy)-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-oneYield 41.6%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Treat a solution of (3-methyl-3H-imidazol-4-yl)-methanol (60.0 mg, 0.54 mmol) in CH2Cl2 with oxalyl chloride (0.15 g, 1.2 mmol) and 2 drops of DMF. Stir at room temperature for 4 h, concentrate, and dissolve in DMF (5.0 mL). Add this solution to a suspension of NaH (62.5 mg, 1.6 mmol) and 2-(4-chloro-phenyl)-5-(4-hydroxy-3-methoxy-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one (200.0 mg, 0.5 mmol) in DMF (5 mL). Stir at room temperature for 2 h, dilute with water, and extract with CH2Cl2 (2×). Combine the organics, dry, and concentrate. Purify by flash chromatography, using 0-10% 2N NH3/MeOH in CH2Cl2, to give the title compound (100.0 mg, 40%). MS (ES+) 481.0 (M+1)+. 1H NMR (400 MHz, CDCl3): δ7.90 (d, 2H, J=8.4 Hz), 7.44 (d, 2H, J=4.0 Hz), 7.41 (s, 1H), 7.07 (s, 1H), 6.97 (d, 1H, J=8.8 Hz), 6.94 (d, 1H, J=2.2 Hz), 6.81 (dd, 1H, J=8.6, 2.4 Hz), 5.04 (s, 2H), 4.07 (t, 2H, J=7.0 Hz), 3.83 (s, 3H), 3.72 (s, 3H), 3.27 (t, 2H, J=6.8 Hz).

Workup

  1. concentrationconcentrate
  2. dissolutiondissolve in DMF (5.0 mL)
  3. additionAdd this solution
  4. stirringStir at room temperature for 2 h
  5. extractionextract with CH2Cl2 (2×)
  6. customCombine the organics, dry
  7. concentrationconcentrate
  8. customPurify by flash chromatography

Sources & evidence

ORD record
ord-5232e42061ee458cb3677c36b4bd6742
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

Loading…