Sodium hydride → Bmy 25368

HRID 1248047Notes

Reaction equation

HRID 1248047 reaction equation
[H-].[Na+].[N:3]1([CH2:9][C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[NH2:17][C:18]1[C:21](=[O:22])[C:20](=[O:23])[C:19]=1[NH:24][CH2:25][CH2:26][CH2:27]Cl>CN(C)C=O>[N:3]1([CH2:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[O:16][CH2:27][CH2:26][CH2:25][NH:24][C:19]2[C:20](=[O:23])[C:21](=[O:22])[C:18]=2[NH2:17])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 8269741-(3-Hydroxybenzyl)piperidineHCID 202808543-Amino-4-[(3-chloropropyl)amino]cyclobut-3-ene-1,2-dione

Product 1

HCID 135156Bmy 25368

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A mixture of sodium hydride (0.16 g; 50% dispersion in oil) in dimethylformamide (20 ml) was cooled to 0° C. To this was added dropwise 3-(piperidinomethyl)phenol (0.6 g) in dimethylformamide (10 ml) and the mixture was allowed to warm to room temperature and stirred for 150 minutes. 1-Amino-2-(3-chloropropylamino)cyclobut-1-ene-3,4-dione (0.6 g) in dimethylformamide (30 ml) was added dropwise and the reaction mixture stirred for 20 hours. On examination by thin layer chromatography it was found that the reaction had not gone to completion. Sodium hydride (0.16 g; 50% dispersion in oil) was added, the reaction mixture stirred for 3 hours at room temperature, then stirred for 3 hours at 65° C. and cooled. The reaction mixture was evaporated under reduced pressure, the residue was treated with dilute sodium hydroxide and extracted into chloroform/methanol (9:1). The chloroform/methanol extracts were combined, dried oer magnesium sulphate, filtered and evaporated under reduced pressure to give the title compound; δppm 1.45 (6H, m), 2.00 (2H, m), 2.40 (4H, m), 3.43 (2H, s), 3.65 (2H, m), 4.03 (2H, t), 6.85 (3H, m), 7.23 (1H, t), 7.50 (broad m) (spectrum consistent with an authentic sample).

Workup

  1. temperatureto warm to room temperature
  2. stirringthe reaction mixture stirred for 20 hours
  3. stirringthe reaction mixture stirred for 3 hours at room temperature
  4. stirringstirred for 3 hours at 65° C.
  5. temperaturecooled
  6. customThe reaction mixture was evaporated under reduced pressure
  7. additionthe residue was treated with dilute sodium hydroxide
  8. extractionextracted into chloroform/methanol (9:1)
  9. dry with materialdried oer magnesium sulphate
  10. filtrationfiltered
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-de3544b941fd49f38b345986353ed513
Source dataset
uspto-grants-1985_06
Patent number
US04521625

Reaction notes

Loading…