Diisobutylaluminumhydride → HCID 59471980, compound

HRID 78631Notes

Reaction equation

HRID 78631 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[NH2:11][C:12]1[C:13]([C:29]2[O:33][C:32]([C:34]3[CH:35]=[C:36]([CH:41]=[CH:42][CH:43]=3)[C:37](OC)=[O:38])=[N:31][N:30]=2)=[N:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24](=[O:28])[N:25]([CH3:27])[CH3:26])=[CH:20][CH:19]=2)=[CH:16][N:17]=1>ClCCl>[NH2:11][C:12]1[N:17]=[CH:16][C:15]([C:18]2[CH:19]=[CH:20][C:21]([C:24]([N:25]([CH3:27])[CH3:26])=[O:28])=[CH:22][CH:23]=2)=[N:14][C:13]=1[C:29]1[O:33][C:32]([C:34]2[CH:43]=[CH:42][CH:41]=[C:36]([CH2:37][OH:38])[CH:35]=2)=[N:31][N:30]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 59472400HCID 59472400, compound

Product 1

HCID 59471980HCID 59471980, compoundYield 18.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Diisobutylaluminium hydride (810.0 μL. of 1 M, 0.8100 mmol) in dichloromethane was added dropwise to a solution of methyl 3-[5-[3-amino-6-[4-(dimethylcarbamoyl)phenyl]pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]benzoate (120 mg, 0.2700 mmol) in CH2Cl2 (6 mL) at 0° C., the solution darkened upon addition. The resulting solution was stirred at 0° C. for 30 min and allowed to warm slowly to room temperature. The reaction mixture was stirred at room temperature for 4 h and then quenched by addition of 1M HCl (3 mL). The resulting mixture was filtered through a Celite pad and washed with dichloromethane (2×5 mL). The layers were separated and the aqueous layer extracted further with dichloromethane (2×10 mL) and combined organic extracts dried over MgSO4 and concentrated in vacuo. The residue was purified using by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were combined and lypholised to give the product as a yellow solid (20.3 mg, 18% yield); 1H NMR (400 MHz, DMSO) d 2.98 (m, 6H), 4.66 (s, 2H), 7.55 (m, 2H), 7.63 (m, 2H), 7.80 (br s, 2H), 8.04 (m, 1H), 8.16 (m, 3H) and 8.99 (s, 1H) ppm; MS (ES+) 417.23

Workup

  1. additionthe solution darkened upon addition
  2. temperatureto warm slowly to room temperature
  3. stirringThe reaction mixture was stirred at room temperature for 4 h
  4. customquenched by addition of 1M HCl (3 mL)
  5. filtrationThe resulting mixture was filtered through a Celite pad
  6. washwashed with dichloromethane (2×5 mL)
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted further with dichloromethane (2×10 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified
  12. customusing by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]

Sources & evidence

ORD record
ord-f79d9ebcd27145c8bdebea428bfe2204
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

Loading…