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

HRID 2036981노트

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HRID 2036981 반응식
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

참가 물질

8

반응물 3

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

생성물 1

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

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
65 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-5083922f67174c65a8fb9ed8124224e5
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575177B2

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