Water → HCID 178500481, compound

HRID 982315Notes

Reaction equation

HRID 982315 reaction equation
I[N:2]1[C:7]([OH:8])=[C:6]2[CH:9]=[CH:10][N:11]=[C:5]2[N:4]=[CH:3]1.[C:12]([C:14]1[CH:33]=[CH:32][C:17]([C:18]([NH:20][C@H:21]([C:28]([O:30][CH3:31])=[O:29])[CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[O:19])=[CH:16][CH:15]=1)#[CH:13].C(N(CC)CC)C.O>CN(C)C=O.[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[OH:8][C:7]1[N:2]([C:13]#[C:12][C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:20][C@H:21]([C:28]([O:30][CH3:31])=[O:29])[CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[O:19])=[CH:32][CH:33]=2)[CH:3]=[N:4][C:5]2=[N:11][CH:10]=[CH:9][C:6]=12

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 15024200Dimethyl 4-ethynylbenzoylglutamateHCID 178515134HCID 178515134, compound

Product 1

HCID 178500481HCID 178500481, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 10 mmol of 3-iodo-4-hydroxypyrrolo[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. There is obtained dimethyl N-[4-(4-hydroxypyrrolo[2,3-d]pyrimidin-3-ylethynyl)benzoyl]-L-glutamate which is purified by chromatography over silica, m.p. 160° C. (dec.). 1NMR (d6 -DMSO) δ1.98-2.15 (m, 2H), 2.45 (t, J=7.5 Hz, 2H), 3.57 (s, 3H), 3.64 (s, 3H), 4.40-4.45 (m, 1H), 7.51 ((d, J=2.5 Hz, 1H), 7.55 (d, J=8.2 Hz), 2H), 7.87 (s, 1H), 7.90 (d, J=8.2 Hz, 1H), 11.97 ((d, J=3.7 Hz, 1H), 12.31 (s, 1H).

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

Sources & evidence

ORD record
ord-051da07a907d4489ab58197aadc740f7
Source dataset
uspto-grants-1991_02
Patent number
US04996206

Reaction notes

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