N-Acetylhomopiperazine → 1-(4-(5-amino-6-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-1,4-diazepan-1-yl)ethanone

HRID 1959336Notes

Reaction equation

HRID 1959336 reaction equation
Br[C:2]1[N:3]=[C:4]([C:9]2[NH:13][C:12]3[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:11]=3[N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[N:19]1([C:26](=[O:28])[CH3:27])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>CN1C(=O)CCC1>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([N:22]2[CH2:23][CH2:24][CH2:25][N:19]([C:26](=[O:28])[CH3:27])[CH2:20][CH2:21]2)=[N:3][C:4]=1[C:9]1[NH:13][C:12]2[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:11]=2[N:10]=1

Participants

4

Reactant 2

HCID 4186202N-AcetylhomopiperazineHCID 580842975-bromo-3-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-amine

Product 1

HCID 461988041-(4-(5-amino-6-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-1,4-diazepan-1-yl)ethanoneYield 56.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of 5-bromo-3-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-amine (100 mg, 0.3288 mmol) and 1-(1,4-diazepan-1-yl)ethanone (701 mg, 4.932 mmol) in NMP (200.0 μL) was heated at 190° C. in the microwave for 2 hours. The reaction mixture was partitioned between DCM and water and the organics separated and concentrated to dryness. The resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound (67.7 mg, 54% Yield). 1H NMR (400.0 MHz, DMSO) d 1.80-1.94 (2H, m), 1.78 (3H, s), 2.43-2.46 (3H, s), 3.40 (2H, m), 3.63-3.83 (5H, m), 3.92 (1H, m), 7.04-7.11 (3H, m), 7.38-7.59 (2H, m), 7.90 (1H, m), 12.37 (1H, m) ppm; MS (ES+) 366

Workup

  1. customThe reaction mixture was partitioned between DCM and water
  2. customthe organics separated
  3. concentrationconcentrated to dryness
  4. customThe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  5. customThe fractions were collected
  6. customfreeze-dried

Sources & evidence

ORD record
ord-d205666ff04c459b9cff696ab5bba166
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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