Acetic Acid → HCID 67444235, compound

HRID 1400885Notes

Reaction equation

HRID 1400885 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]=[CH:26][N:27]([CH2:29][CH:30]=O)[CH:28]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1C(=O)CCC1>[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]=[CH:26][N:27]([CH2:29][CH2:30][N:37]6[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]6)[CH:28]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)=[O:6])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86658579HCID 86658579, compound

Product 1

HCID 67444235HCID 67444235, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 264 (300 mg, 0.66 mmol), N-methylpiperazine (74 μl, 0.66 mmol) and AcOH (76 μl, 1.33 mmol) in NMP (10 mL) was added sodium triacetoxyborohydride (422 mg, 1.99 mmol) and the reaction mixture was stirred for 2.5 days at RT. The reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with DCM. The organic extract was successively washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 40 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 15/85 over 20 CV) and by Gilson (Phenomenex, Luna 15μ, C18(2) 100A, 250×50.0 mm, 15 μm; 0.05% of formic acid in both MeOH/water:20/80 to 95/5 over 60 min, flow; 30 mL/min) to afford the title compound 266 (180 mg, 0.33 mmol, 51% yield, di-formate salt) as a white solid.

Workup

  1. customThe reaction mixture was quenched with saturated sodium bicarbonate solution
  2. extractionextracted with DCM
  3. extractionThe organic extract
  4. washwas successively washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 40 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 15/85 over 20 CV) and by Gilson (Phenomenex, Luna 15μ, C18(2) 100A, 250×50.0 mm, 15 μm
  9. wait0.05% of formic acid in both MeOH/water:20/80 to 95/5 over 60 min

Sources & evidence

ORD record
ord-c090daf8fce247bea4a9b4ef2803f25c
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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