Triethylamine → HCID 178471582, compound

HRID 1108281Notes

Reaction equation

HRID 1108281 reaction equation
[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:20])[C:11]2[CH:17]=[C:16]([C:18]#[CH:19])[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].Br[C:22]1[S:23][CH:24]=[C:25]([C:27]([NH:29][C@H:30]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:28])[N:26]=1.C(N(CC)CC)C>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:20])[C:11]2[CH:17]=[C:16]([C:18]#[C:19][C:22]3[S:23][CH:24]=[C:25]([C:27]([NH:29][C@H:30]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:28])[N:26]=3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 54224793diethyl N-(2-bromo-4-thiazolylcarbonyl)-L-glutamateHCID 178437079HCID 178437079, compound

Product 1

HCID 178471582HCID 178471582, compoundYield 67.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To a 100 mL 14/20 round bottom flask under an argon atmosphere were added 0.316 g (1.17 mmol) of 2 -pivaloylamino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine suspended in 10 mL of acetonitrile, followed by the addition of 0.47 g (1.2 mmol) of diethyl N-(2-bromo-4-thiazolylcarbonyl)-L-glutamate, 0.14 g (0.12 mmol) of tetrakis(triphenylphosphine)palladium (0), 0.046 g (0.24 mmol) of copper (I) iodide, and 0.35 mL (2.5 mmol) of triethylamine with an additional 10 mL of acetonitrile. The reaction was heated to reflux for 2 hours The volatiles were removed in vacuo, and the residue purified using silica gel flash chromatography, eluting with a step gradient of 100% chloroform to 2% methanol/chloroform to give 0.46 g (67%) of diethyl N-{2-[2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-ylethynyl]-4-thiazolylcarbonyl}-L-glutamate as an off-white solid, m.p. 201-202° C. (dec). Rf =0.28 (4% methanol/chloroform). 1H NMR (300 MHz, DMSO-d6) δ 1.12-1.29 (m, 15H), 2.05-2.15 (m, 1H), 2.37 (t, J=7.2 Hz, 2H), 3.98-4.13 (m, 4H), 4.45-4.49 (m, 1H), 8.47 (s, 1H), 8.61 (d, J=1.8 Hz, 1H), 8.84 (d, J=8.1 Hz, 1H), 9.07 (d, J=1.9 Hz, 1H)

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2 hours The volatiles
  3. customwere removed in vacuo
  4. customthe residue purified
  5. washeluting with a step gradient of 100% chloroform to 2% methanol/chloroform

Sources & evidence

ORD record
ord-f7826e9d14d246bdab06d72dae5f0981
Source dataset
uspto-grants-2000_05
Patent number
US06066639

Reaction notes

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