Diisopropylethylamine → N2-(3-Chloro-phenyl)-N4-[3-(4-methanesulfonyl-piperazin-1-yl)-propyl]-pyrimidine-2,4-diamine

HRID 1803930Notes

Reaction equation

HRID 1803930 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[N:3]=1.CCN(C(C)C)C(C)C.[CH3:25][S:26]([N:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][CH2:37][NH2:38])[CH2:31][CH2:30]1)(=[O:28])=[O:27]>C1COCC1>[Cl:15][C:11]1[CH:10]=[C:9]([NH:8][C:4]2[N:3]=[C:2]([NH:38][CH2:37][CH2:36][CH2:35][N:32]3[CH2:33][CH2:34][N:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH2:30][CH2:31]3)[CH:7]=[CH:6][N:5]=2)[CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 287059553-(4-(Methylsulfonyl)piperazin-1-yl)propan-1-amineHCID 590282434-chloro-N-(3-chlorophenyl)pyrimidin-2-amine

Product 1

HCID 24797880N2-(3-Chloro-phenyl)-N4-[3-(4-methanesulfonyl-piperazin-1-yl)-propyl]-pyrimidine-2,4-diamineYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 4-chloro-N-(3-chlorophenyl)pyrimidin-2-amine (0.2 g, 0.837 mmol) in THF (10 mL) is added DIPEA (0.29 mL, 1.67 mmol) followed by 3-(4-(methylsulfonyl)piperazin-1-yl)propan-1-amine, 25, (0.0.369 g, 1.67 mmol). The resulting mixture is refluxed for 12 hours after which the reaction mixture is cooled to room temperature and the solvent removed in vacuo. To the resulting residue is added water (50 mL) and the solution is washed with EtOAc (3×100 mL). The combined organic layers are dried (MgSO4) and concentrated in vacuo. The residue which is obtained is purified over silica (10% MeOH in CH2Cl2) to afford 0.129 g (50% yield) of the desired compound. 1H NMR (DMSO-d6, 300 MHz) δ1.71 (m, 2H), 2.39-2.45 (m, 6H), 2.84 (s, 3H), 3.08 (m, 4H), 3.38 (m, 2H), 5.96 (d, J=5.7 Hz, 1H), 6.87 (d, J=7.8 Hz, 1H), 7.18-7.27 (m, 2H), 7.58 (d, J=7.5 Hz, 1H), 7.81 (bs, 1H), 8.12 (bs, 1H), 9.18 (s, 1H). MS (ESI, pos. ion) m/z: 425 (M+1). HRMS calcd for C18H25ClN6O2S, 425.1526 m/z (M+H)+; observed 425.1512 m/z.

Workup

  1. temperatureThe resulting mixture is refluxed for 12 hours after which the reaction mixture
  2. customthe solvent removed in vacuo
  3. additionTo the resulting residue is added water (50 mL)
  4. washthe solution is washed with EtOAc (3×100 mL)
  5. dry with materialThe combined organic layers are dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue which is obtained
  8. customis purified over silica (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-3469a539a61449548084ff7d7fed9386
Source dataset
uspto-grants-2013_01
Patent number
US08354407B2

Reaction notes

Loading…