Sodium hydride → HCID 53745238, compound

HRID 1383832Notes

Reaction equation

HRID 1383832 reaction equation
[C:1]1([C:7]2[N:11]3[NH:12][C:13](=[O:22])[C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:15][C:10]3=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Cl[CH2:26][C:27]1[N:28]=[N:29][N:30]([CH3:32])[N:31]=1>CN(C=O)C>[CH3:32][N:30]1[N:29]=[N:28][C:27]([CH2:26][O:22][C:13]2[C:14]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:15][C:10]3[N:11]([C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:8][N:9]=3)[N:12]=2)=[N:31]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 122050815-chloromethyl-2-methyl-2H-tetrazoleHCID 21187496HCID 21187496, compound

Product 1

HCID 53745238HCID 53745238, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To the product from Example 73, Step a (0.15 g, 0.52 mmol) in anhydrous DMF (5 ml) was added sodium hydride (60% dispersion in oil, 31.2 mg, 0.780 mmol) and the mixture was stirred under nitrogen at room temperature for 45 min then at 80° C. for another 20 min. After allowing to cool, a solution of 5-chloromethyl-2-methyl-2H-tetrazole (Moderhack, D., Chem. Ber., 1975, 108, 887-896) (0.103 g, 0.780 mmol) in anhydrous DMF (4 ml) was added and the mixture was stirred at room temperature under nitrogen for 1.5 h, then at 80° C. for 17 h. The mixture was then partitioned between water (30 ml) and ethyl acetate (40 ml). The aqueous layer was further extracted with ethyl acetate (9×40 ml) and the combined organic extracts were dried (MgSO4), and evaporated in vacuo. The residue was recrystallised from EtOAc—CH2Cl2—MeOH to afford 0.1002 g (50%) of the title compound as a white solid: mp 228-233° C.; 1H NMR (360 MHz, CDCl3) δ 4.36 (3H, s), 5.79 (2H, s), 7.47-7.60 (8H, m), 8.07 (1H, s), 8.48 (2H, m); MS (ES+) m/e 385 [MH]+. Anal. Found C, 62.01; H, 4.13; N, 28.92. C20H16N8O. 0.17H2O requires C, 62.00; H, 4.25; N, 28.92%.

Workup

  1. waitat 80° C. for another 20 min
  2. temperatureto cool
  3. stirringthe mixture was stirred at room temperature under nitrogen for 1.5 h
  4. waitat 80° C. for 17 h
  5. customThe mixture was then partitioned between water (30 ml) and ethyl acetate (40 ml)
  6. extractionThe aqueous layer was further extracted with ethyl acetate (9×40 ml)
  7. dry with materialthe combined organic extracts were dried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was recrystallised from EtOAc—CH2Cl2—MeOH

Sources & evidence

ORD record
ord-321ff3880c70446a8ceed030e4deaa99
Source dataset
uspto-grants-2001_07
Patent number
US06255305B1

Reaction notes

Loading…