2-Aminothiazole → 5-(4-(Ethylsulfonyl)piperazin-1-yl)-3-(imidazo[2,1-b]thiazol-6-yl)pyrazin-2-amine

HRID 1959379Notes

Reaction equation

HRID 1959379 reaction equation
[NH2:1][C:2]1[C:3]([C:19](=O)[CH2:20]Br)=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[CH:6][N:7]=1.[CH:23]1[N:27]=[C:26]([NH2:28])[S:25][CH:24]=1>CCO>[CH2:17]([S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[N:4]=[C:3]([C:19]3[N:28]=[C:26]4[N:27]([CH:20]=3)[CH:23]=[CH:24][S:25]4)[C:2]([NH2:1])=[N:7][CH:6]=2)[CH2:9][CH2:10]1)(=[O:16])=[O:15])[CH3:18]

Participants

4

Reactant 2

HCID 21552-AminothiazoleHCID 866620741-(3-Amino-6-(4-(ethylsulfonyl)piperazin-1-yl)pyrazin-2-yl)-2-bromoethanone

Product 1

HCID 461998715-(4-(Ethylsulfonyl)piperazin-1-yl)-3-(imidazo[2,1-b]thiazol-6-yl)pyrazin-2-amineYield 156.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-[3-amino-6-(4-ethylsulfonylpiperazin-1-yl)pyrazin-2-yl]-2-bromo-ethanone (35 mg, 0.08922 mmol) was suspended in EtOH (2 mL) and 2 aminothiazole (8.935 mg, 0.08922 mmol) was added. The mixture was heated at reflux for 4 hours and then allowed to cool to ambient temperature. The solution was filtered through a 0.45 μnm PTFE filter and the solvent removed under a stream of nitrogen. 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 and freeze-dried to give the title compound (55 mg, 10% Yield). 1H NMR (400.0 MHz, DMSO) d 1.14 (t, J=7.3 Hz, 3H), 3.01 (q, J=7.4 Hz, 2H), 3.21-3.23 (m, 4H), 3.34-3.36 (m, 4H), 7.28 (d, J=4.4 Hz, 1H), 7.67 (s, 1H), 7.89 (d, J=4.4 Hz, 1H) and 8.23 (s, 1H) ppm; MS (ES+) 394.0

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 hours
  3. filtrationThe solution was filtered through a 0.45 μnm PTFE
  4. filtrationfilter
  5. customthe solvent removed under a stream of nitrogen
  6. 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]
  7. customThe fractions were collected
  8. customfreeze-dried

Sources & evidence

ORD record
ord-4e69947e492b44b384b4b1f44711960d
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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