Water → HCID 178418681, compound

HRID 6526Notes

Reaction equation

HRID 6526 reaction equation
I[N:2]1[C:7]([OH:8])=[C:6]2[CH:9]=[C:10]([NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[N:11]=[C:5]2[N:4]=[CH:3]1.[C:19]([C:21]1[CH:40]=[CH:39][C:24]([C:25]([NH:27][C@H:28]([C:35]([O:37][CH3:38])=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])=[CH:23][CH:22]=1)#[CH:20].C(N(CC)CC)C.O>CN(C)C=O.[Cu]I>[OH:8][C:7]1[N:2]([C:20]#[C:19][C:21]2[CH:22]=[CH:23][C:24]([C:25]([NH:27][C@H:28]([C:35]([O:37][CH3:38])=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])=[CH:39][CH:40]=2)[CH:3]=[N:4][C:5]2=[N:11][C:10]([NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:9][C:6]=12

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 15024200Dimethyl 4-ethynylbenzoylglutamateHCID 178418587HCID 178418587, compound

Product 1

HCID 178418681HCID 178418681, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3.6 g (10 mmol) of well-dried 3-iodo-4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidine in 40 mL of dimethylformamide are added 4.0 g (13.19 mmol) of dimethyl N-(4-ethynylbenzoyl)-L-glutamate, 0.38 g of copper (I) iodide, 3 mL of triethylamine, and 1.0 g of tetrakis-(triphenylphosphine)palladium. This mixture is stirred at ambient temperatures for two hours and then poured into 500 mL of water. The solid is collected by filtration, air dried, and then refluxed in 200 mL of methanol. The mixture is cooled and the solid collected by filtration, dissolved in two liters of 10% methanol in methylene chloride, and chromatographed over silica. Initial black bands are rechromatographed and the combined colorless bands from the first and second runs are evaporated to give 3.5 g of dimethyl N-[4-(4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidin-3-ylethynyl)benzoyl]-L-glutamate which can be purified further by recrystallization from 50% methanol in methylene chloride.

Workup

  1. filtrationThe solid is collected by filtration, air
  2. customdried
  3. temperaturerefluxed in 200 mL of methanol
  4. temperatureThe mixture is cooled
  5. filtrationthe solid collected by filtration
  6. dissolutiondissolved in two liters of 10% methanol in methylene chloride
  7. customchromatographed over silica
  8. customInitial black bands are rechromatographed
  9. customthe combined colorless bands from the first and second runs are evaporated

Sources & evidence

ORD record
ord-08c77ae1ea2d4cbc9b60678aaa348fec
Source dataset
uspto-grants-1993_09
Patent number
US05248775

Reaction notes

Loading…