Sodium Carbonate → HCID 19921680, compound

HRID 1463361Notes

Reaction equation

HRID 1463361 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[C:25]([O:26][CH3:27])=[CH:24][N:23]=[CH:22][N:21]=2)[CH2:16][CH2:15]1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:34][CH2:35][CH2:36][CH2:37][C:38](Cl)=[O:39]>CC(C)=O>[Cl:34][CH2:35][CH2:36][CH2:37][C:38]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[C:25]([O:26][CH3:27])=[CH:24][N:23]=[CH:22][N:21]=2)[CH2:16][CH2:15]1)=[O:39]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 783704-Chlorobutyryl chlorideHCID 199620373-[3-[4-(5-Methoxy-4-pyrimidyl)-1-piperazinyl]propyl]-5-amino-1H-indole

Product 1

HCID 19921680HCID 19921680, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of 1-[3-[5-amino-1-H-indol-3-yl]propyl]-4-(5-methoxy-4-pyrimidinyl)piperazine (2.3g, 6.3 mmol), and sodium carbonate (0.67 g, 6.3 mmol) in 25 mL of acetone, cooled to 0° C., was added dropwise 4-chlorobutyryl chloride (0.89 g, 6.3 mmol). Additional acetone (10 mL) was added and the suspension was stirred for 19 h at 23° C. The insoluble material was separated by filtration and the acetone was removed in vacuo. The crude material was dissolved in EtOAc, and the solution was washed with water, dried (brine, MgSO4), filtered, and concentrated in vacuo to give crude 1-[3-[5-[4-chlorobutyrylamino]-1-H-indol-3-yl]propyl]-4-(5-methoxy-4-pyrimidinyl)piperazine (1.98 g, 4.2 mmol, 67%) as a gum. Sodium ethoxide (0.67 mL, 2.1 mmol, 21% in ethanol) was added dropwise to a solution of crude 1-[3-[5-[4-chlorobutyrylamino]-1-H-indol-3-yl]propyl]-4-(5-methoxy-4-pyrimidinyl)piperazine (1.0 g, 2.1 mmol) in ethanol (5 mL). After the addition, the reaction mixture was heated at 78° C. for 90 min and then cooled to room temperature. The insoluble solid was separated and the filtrate was concentrated in vacuo. Silica gel column chromatography (95:5:0.5 CH2Cl2 -MeOH-30% NH4OH) afforded 1-[3-[5-[2-pyrrolidinone-1-yl]-1-yl]-1-H-indol-3-yl]propyl]-4-(5-methoxy-4-pyrimidinyl)piperazine (0.33 g, 0.76 mmol, 36%). The free base (0.25 g, 0.58 mmol) was dissolved in a minimum volume of acetonitrile. A concentrated solution of oxalic acid (0.052 g, 0.58 mmol) in CH3CN was added with stirring. The precipitate was separated by filtration, washed sparingly with CH3CN, and dried at 70° C. in vacuo overnight to give the title compound (0.17 g, 56%): mp 100°-101° C. Anal. Calcd for C24H30N6O2.1.0 C2H2O4.1.15 H2O: C, 57.26; H, 6.34; N, 15.41. Found: C, 56.90; H, 5.96; N, 15.51.

Workup

  1. customThe insoluble material was separated by filtration
  2. customthe acetone was removed in vacuo
  3. dissolutionThe crude material was dissolved in EtOAc
  4. washthe solution was washed with water
  5. dry with materialdried (brine, MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ff45ecb66ddb4101958ae8446c4867d1
Source dataset
uspto-grants-1994_04
Patent number
US05300506

Reaction notes

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