1-Methylpiperazine → HCID 67441978, compound

HRID 1400927Notes

Reaction equation

HRID 1400927 reaction equation
[CH:1]1([NH:4][C:5](=[O:47])[NH:6][C:7]2[CH:45]=[CH:44][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][N:28]6[CH2:33][CH2:32][CH:31]([NH:34][C:35](=O)[O:36]C7C=CC=CC=7)[CH2:30][CH2:29]6)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:46])[CH:8]=2)[CH2:3][CH2:2]1.[CH3:48][N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.C([O-])(O)=O.[Na+]>CN(C=O)C.[Cl-].[Na+].O>[CH:1]1([NH:4][C:5](=[O:47])[NH:6][C:7]2[CH:45]=[CH:44][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][N:28]6[CH2:29][CH2:30][CH:31]([NH:34][C:35]([N:52]7[CH2:53][CH2:54][N:49]([CH3:48])[CH2:50][CH2:51]7)=[O:36])[CH2:32][CH2:33]6)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:46])[CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 67442475HCID 67442475, compound

Product 1

HCID 67441978HCID 67441978, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
92.5 °C

Procedure

To a solution of the phenylcarbamate 356 (0.11 g, 0.169 mmol) in DMF at RT was added the N-methylpiperazine (0.057 mL, 0.51 mmol). The reaction mixture was heated at 90-95° C. for 2 hours, cooled to RT then treated with brine and saturated NaHCO3 solution. A precipitate was formed which was collected by filtration and dried. The crude material was purified by flash column chromatography, eluent 12 to 30% MeOH (containing 2% ammonia) in DCM, to afford the title compound 357 (0.088 g, 79% yield). 1H NMR (400 MHz, CD3OD-d6) δ (ppm): 8.65 (d, J=1.4 Hz, 1H); 8.47 (d, J=5.5 Hz, 1H); 8.15-8.11 (m, 2H); 7.98 (dd, J=8.2, 2.0 Hz, 1H); 7.67 (dd, J=13.1, 2.3 Hz, 1H); 7.30 (t, J=9.0 Hz, 1H); 7.20 (br. d, J=9.0 Hz, 1H); 6.64 (d, J=5.5 Hz 1H); 3.94 (s, 2H); 3.68-3.65 (m, 1H); 3.57 (br. s, 4H); 3.18 (br. d, J=10.4 Hz, 2H); 2.89 (br. s, 4H); 2.65 (s, 3H); 2.63-2.58 (m, 3H); 1.98 (br. d, J=11.7 Hz, 2H); 1.69 (br. d, J=11.0 Hz, 2H); 0.79-0.74 (m, 2H); 0.55-0.52 (m, 2H). [Signals of NH-protons are not seen]. MS (m/z): 659.5 (M+1)+

Workup

  1. temperaturecooled to RT
  2. customA precipitate was formed which
  3. filtrationwas collected by filtration
  4. customdried
  5. customThe crude material was purified by flash column chromatography, eluent 12 to 30% MeOH (containing 2% ammonia) in DCM

Sources & evidence

ORD record
ord-d92978b1d0cc40c1b0f86e44ca0964ba
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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