Triethylamine → HCID 131730835, compound

HRID 1898610Notes

Reaction equation

HRID 1898610 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:35])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23](Br)[N:24]=3)[N:19](COCC[Si](C)(C)C)[CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[N:2].C(N(CC)CC)C.[C:43]([Si:45]([CH3:48])([CH3:47])[CH3:46])#[CH:44]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:1]([CH:3]1[CH2:4][CH2:5][N:6]([C:9](=[O:35])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:44]#[C:43][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:7][CH2:8]1)#[N:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 866578732-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Product 1

HCID 131730835HCID 131730835, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (0.50 g, 0.89 mmol) (5:1 mix of 5-Br and 5-Cl) in DMF (3 mL) were added sequentially triethylamine (0.50 mL, 3.56 mmol), ethynyltrimethylsilane (0.15 mL, 1.07 mmol), Pd(PPh3)2Cl2 (31.2 mg, 0.045 mmol), and copper (I) iodide (8.5 mg, 0.045 mmol). Upon the addition of CuI all solids dissolved. The reaction mixture was stirred at room temperature for 30 min then heated at 50° C. for 1 h. The reaction mixture was cooled to room temperature, quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes) to isolate 430 mg (83%) of 542-trimethylsilanyl-ethoxymethyl)-2-trimethylsilanylethynyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a brown foamy solid. NMR showed a trace of unreacted 5-Cl pyrrolopyrazine present.

Workup

  1. dissolutiondissolved
  2. temperaturethen heated at 50° C. for 1 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customquenched with water
  5. extractionextracted with EtOAc (3×)
  6. washThe combined organics were washed with water (3×) and brine
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f5266aa118e24f30ad1e84f45f1a9490
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

Loading…