Propargyl bromide → Diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)-amino]benzoyl}-L-glutamate

HRID 1289229Notes

Reaction equation

HRID 1289229 reaction equation
[CH3:1][C:2]1[N:11]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[C:10](=[O:20])[C:9]2[C:4](=[CH:5][C:6]3[CH2:23][CH2:22][CH:21]([NH:24][C:25]4[CH:46]=[CH:45][C:28]([C:29]([NH:31][C@H:32]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:30])=[CH:27][CH:26]=4)[C:7]=3[CH:8]=2)[N:3]=1.[CH2:47](Br)[C:48]#[CH:49].C(=O)([O-])[O-].[Ca+2]>CC(N(C)C)=O>[CH3:1][C:2]1[N:11]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:16])([CH3:17])[CH3:18])[C:10](=[O:20])[C:9]2[C:4](=[CH:5][C:6]3[CH2:23][CH2:22][CH:21]([N:24]([C:25]4[CH:26]=[CH:27][C:28]([C:29]([NH:31][C@H:32]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:30])=[CH:45][CH:46]=4)[CH2:49][C:48]#[CH:47])[C:7]=3[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 10112Calcium CarbonateHCID 10532105diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoyl}-L-glutamate

Product 1

HCID 11802616Diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)-amino]benzoyl}-L-glutamate

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoyl}-L-glutamate (13.5 g), propargyl bromide (32 g), calcium carbonate (10.7 g) and DMA (250 ml) was stirred and heated to 110° C. for 5 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography using increasingly polar mixtures of hexane and ethyl acetate as eluant. There was thus obtained diethyl -{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)--amino]benzoyl }-L-glutamate as a foam (9 g).

Workup

  1. customThe mixture was evaporated
  2. customthe residue was partitioned between ethyl acetate and water
  3. washThe organic phase was washed with water
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. temperatureusing increasingly polar mixtures of hexane and ethyl acetate as eluant

Sources & evidence

ORD record
ord-7af50039a90441b9b80716dec9b4974b
Source dataset
uspto-grants-1998_05
Patent number
US05747499

Reaction notes

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