Triethylamine → (S)-tert-butyl 3-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

HRID 516161Notes

Reaction equation

HRID 516161 reaction equation
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:24]([C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=1)#[CH:25].C(N(CC)CC)C.C(OCC)(=O)C>C1COCC1.[Cu]I.O>[NH2:1][C:2]1[C:3]2[C:10]([C:25]#[C:24][C:26]3[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=3)=[CH:9][N:8]([C@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 46613211-Ethynyl-3,5-dimethoxybenzeneHCID 89870889(S)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 89870927(S)-tert-butyl 3-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

PdCl2(dppf)2CH2Cl2 (122 mg) was added to a mixture of (S)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (660 mg) obtained in Step 2 above, 1-ethynyl-3,5-dimethoxybenzene (374 mg), copper (I) iodide (44 mg), and triethylamine (2.0 ml) in THF (15 ml). After nitrogen purging, the resulting mixture was stirred at 80° C. for 3.5 hours. Ethyl acetate and water were added to the reaction mixture to separate the organic layer. After washing with a saturated sodium chloride solution, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a colorless, amorphous substance (714 mg). Physical properties: m/z [M+H]+ 464.1

Workup

  1. customto separate the organic layer
  2. washAfter washing with a saturated sodium chloride solution
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d12f1e30465345deb23e0f64800b958f
Source dataset
uspto-grants-2015_08
Patent number
US09108973B2

Reaction notes

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