Dimethylamine → 2-{4-[4-(2-Dimethylaminoacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

HRID 1441310Notes

Reaction equation

HRID 1441310 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[N:6]1([C:12]2[CH:33]=[CH:32][C:15]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[N:27]([CH:28]([CH3:30])[CH3:29])[C:26]([CH3:31])=[N:25][CH:24]=4)[CH:20]=[CH:19][N:18]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.[CH2:34]([N:36](CC)[CH2:37]C)C.CNC.C1COCC1>C(Cl)Cl>[CH3:34][N:36]([CH3:37])[CH2:2][C:3]([N:9]1[CH2:10][CH2:11][N:6]([C:12]2[CH:33]=[CH:32][C:15]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[N:27]([CH:28]([CH3:30])[CH3:29])[C:26]([CH3:31])=[N:25][CH:24]=4)[CH:20]=[CH:19][N:18]=3)=[CH:14][CH:13]=2)[CH2:7][CH2:8]1)=[O:4]

Participants

7

Reactant 5

HCID 674DimethylamineHCID 6577Chloroacetyl chlorideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 686857662-[4-(Piperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Product 1

HCID 445786492-{4-[4-(2-Dimethylaminoacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidineYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Chloroacetyl chloride (50 μl, 0.65 mmol) was added dropwise to a stirred solution of 2-[4-(piperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Example 20; 200 mg, 0.53 mmol) and triethylamine (90 μl, 0.65 mmol) in DCM (5 ml) at room temperature. After 50 minutes, 2M dimethylamine in THF solution (2 ml, 4 mmol) was added and the reaction was stirred for 5 hours before evaporating under reduced pressure. Chromatography on neutral alumina (activity II) with MeOH:DCM (1:99 to 3:97) gave material which required further purification on silica gel with MeOH:DCM:7N NH3MeOH (3:97:0.0025 to 10:90:0.0025) to give the title compound as a yellow foam. (150 mg 60% yield). NMR: 1.39 (d, 6H), 2.19 (s, 6H), 2.46 (s, 3H), 3.02 (b t, 2H), 3.06 (b t, 2H), 3.59 (b t, 2H), 3.68 (b t, 2H), 5.69 (septuplet, 1H), 6.92 (d, 2H), 6.94 (d, 1H), 7.39 (s, 1H), 7.47 (d, 2H), 8.31 (d, 1H), 9.17 (s, 1H); m/z 463.

Workup

  1. custombefore evaporating under reduced pressure
  2. customChromatography on neutral alumina (activity II) with MeOH:DCM (1:99 to 3:97) gave material which required
  3. customfurther purification on silica gel with MeOH

Sources & evidence

ORD record
ord-541d57449077418f83c3d7750a0e482d
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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