Triethylamine → Tert-butyl cyclopropyl(3-formyl-6-((trimethylsilyl)ethynyl)imidazo[1,2-a]pyrazin-8-yl)carbamate

HRID 624762Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 624762
C(N(CC)CC)C.Br[C:9]1[N:10]=[C:11]([N:20]([CH:28]2[CH2:30][CH2:29]2)[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:12]2[N:13]([C:15]([CH:18]=[O:19])=[CH:16][N:17]=2)[CH:14]=1.[CH3:31][Si:32]([C:35]#[CH:36])([CH3:34])[CH3:33]>CN(C=O)C.CCOC(C)=O.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>[CH:28]1([N:20]([C:11]2[C:12]3[N:13]([C:15]([CH:18]=[O:19])=[CH:16][N:17]=3)[CH:14]=[C:9]([C:36]#[C:35][Si:32]([CH3:34])([CH3:33])[CH3:31])[N:10]=2)[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:30][CH2:29]1

Komponenten

8

Edukt 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 86714607Tert-butyl 6-bromo-3-formylimidazo[1,2-a]pyrazine-8-yl(cyclopropyl)carbamate

Produkt 1

HCID 86714609Tert-butyl cyclopropyl(3-formyl-6-((trimethylsilyl)ethynyl)imidazo[1,2-a]pyrazin-8-yl)carbamateAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

Triethylamine (912 μL, 6.56 mmol) was added to tert-butyl 6-bromo-3-formylimidazo[1,2-a]pyrazine-8-yl(cyclopropyl)carbamate (250 mg, 0.66 mmol) dissolved in anhydrous DMF (2.2 mL) in a 15 mL pressure tube. The solution was degassed with a stream of N2 for 10 min. Trimethylsilylacetylene (927 μL, 6.56 mmol), Pd(PPh3)4 (76 mg, 0.07 mmol), and copper(I) iodide (25 mg, 0.13 mmol) were added and the reaction was sealed and heated to 65° C. for 24 h. The reaction was diluted with EtOAc (50 mL) and then washed with 10% brine (4×50 mL) and brine (50 mL). The organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (30% EtOAc/hexanes) to give tert-butyl cyclopropyl(3-formyl-6-((trimethylsilyl)ethynyl)imidazo[1,2-a]pyrazin-8-yl)carbamate (186 mg, 71%) as a brown foamy solid. LCMS (ES): >95% pure, m/z 400 [M+1]+.

Aufarbeitung

  1. customThe solution was degassed with a stream of N2 for 10 min
  2. customthe reaction was sealed
  3. washwashed with 10% brine (4×50 mL) and brine (50 mL)
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash column chromatography (30% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-2757c8ecbda74554bb5df4e993ed0b02
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303033B2

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