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

HRID 624762Notes

Reaction equation

HRID 624762 reaction equation
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

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-2757c8ecbda74554bb5df4e993ed0b02
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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