Potassium Carbonate → (R)-2-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-quinazolin-3-yl]-pentanoic acid methyl ester

HRID 388473Notes

Reaction equation

HRID 388473 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C@H:4]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][C:9]1=[O:19])[CH2:5][CH2:6][CH3:7].C[C:22]1[C:23]([CH3:38])=[C:24](C)[C:25]([CH3:36])=[C:26]2[C:30]=1[N:29]([CH3:31])[C:28](C)=[C:27]2[CH2:33]NI.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:20])[C@H:4]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([CH2:33][C:27]2[C:26]3[C:30](=[CH:22][C:23]([CH3:38])=[CH:24][C:25]=3[CH3:36])[N:29]([CH3:31])[CH:28]=2)[C:9]1=[O:19])[CH2:5][CH2:6][CH3:7]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68726798(R)-2-(2,4-Dioxo-1,4-dihydro-2H-quinazolin-3-yl)-pentanoic acid methyl esterHCID 131730211trimethyl-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-amino iodide

Product 1

HCID 68745323(R)-2-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-quinazolin-3-yl]-pentanoic acid methyl esterYield 80.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-2-(2,4-Dioxo-1,4-dihydro-2H-quinazolin-3-yl)-pentanoic acid methyl ester (50 mg, 0.18 mmol) (prepared according to example 1, steps 1-3) in DMF (10 mL) are added trimethyl-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-amino iodide (97 mg, 0.27 mmol) and K2CO3 (50 mg, 0.36 mmol) at room temperature. The solution is heated to 100° C. for 4 hours. The solution is cooled and is extracted with water and EtOAc. The combined organic layer is dried with MgSO4 and is filtered. The filtrate is concentrated and the residue is purified by flash chromatography with 20% EtOAc in Hexane as the eluent to afford (R)-2-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-quinazolin-3-yl]-pentanoic acid methyl ester (65 mg, 80%) as a white foam.

Workup

  1. temperatureThe solution is cooled
  2. extractionis extracted with water and EtOAc
  3. dry with materialThe combined organic layer is dried with MgSO4
  4. filtrationis filtered
  5. concentrationThe filtrate is concentrated
  6. customthe residue is purified by flash chromatography with 20% EtOAc in Hexane as the eluent

Sources & evidence

ORD record
ord-8e2484668a184771af1b0793a73d1ee9
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

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