Dimethylformamide → Tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718584

반응식

HRID 718584 반응식
[C:1]([C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[N:7][N:6]2[C:17]=1[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)#[CH:2].Br[C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1.CN(C=O)C.CCN(C(C)C)C(C)C>[Cu]I.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.O>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([C:17]([C:18]4[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])=[CH:20][CH:19]=4)=[C:3]([C:1]#[C:2][C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[N:33]=4)[N:4]=3)[N:7]=[CH:8][CH:9]=2)[CH2:12][CH2:13]1

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27627562-BromoquinolineHCID 117732463tert-Butyl 4-(2-ethynyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

생성물 1

HCID 117728418Tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

실험 절차

A mixture of compound 17a (0.23 g, 0.57 mmol) and 2-bromoquinoline (1.0 g, 4.8 mmol) in a vial was evacuated and back flushed with Argon. Dry DMF (5 mL) and DIEA (0.99 mL, 5.7 mmol) were added via syringe and the mixture was deoxygenated by bubbling Argon gas through the stirred solution for 5 min. To the mixture were added CuI (5.4 mg, 0.028 mmol) and dichlorobis(triphenylphosphine)palladium(II) (40 mg, 0.057 mmol). The resulting mixture was stirred at rt for 1 h, and was poured into water (50 mL). The mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water (20 mL) and brine (2×20 mL). The organic layer was concentrated, and the resulting residue was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane) to give tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate as a yellow solid.

후처리

  1. customwas evacuated
  2. customback flushed with Argon
  3. customthe mixture was deoxygenated
  4. customby bubbling Argon gas through the stirred solution for 5 min
  5. extractionThe mixture was extracted with EtOAc (3×30 mL)
  6. washThe combined organic extracts were washed with water (20 mL) and brine (2×20 mL)
  7. concentrationThe organic layer was concentrated
  8. customthe resulting residue was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-730fdae97bef4084a60a9d91da0963ba
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193736B2

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