Water → 4-(5-Bromo-2-(quinolin-2-ylethynyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

HRID 1772719Notes

Reaction equation

HRID 1772719 reaction equation
[Br:1][C:2]1[N:7]2[CH:8]=[C:9]([C:11]#[CH:12])[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1.Br[C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1.CCN(C(C)C)C(C)C.O>CN(C=O)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>[Br:1][C:2]1[N:7]2[CH:8]=[C:9]([C:11]#[C:12][C:20]3[CH:29]=[CH:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)[N:10]=[C:6]2[C:5]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27627562-BromoquinolineHCID 1177279194-(5-Bromo-2-ethynylimidazo[1,2-a]pyrazin-8-yl)morpholine

Product 1

HCID 1177323014-(5-Bromo-2-(quinolin-2-ylethynyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

Reagents, catalysts & solvents 3

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

Procedure

To a stirred solution of compound 80a (200 mg, 0.7 mmol) and 2-bromoquinoline (0.800 mg, 4 mmol) in dry DMF (5 mL) and DIEA (0.7 mL, 4 mmol) under an Argon gas atmosphere, CuI (12 mg, 0.06 mmol) and (Ph3P)2PdCl2 (46 mg, 0.06 mmol) were added. The reaction was stirred at rt overnight, poured into water (50 mL) and extracted with DCM (3×30 mL). The combined organic extracts were washed with water (20 mL), brine (2×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0-50% EtOAc/heptanes) to give compound 80b as an off-white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C21H16BrN5O: 434.0 (M+H). found: 434.2.

Workup

  1. extractionextracted with DCM (3×30 mL)
  2. washThe combined organic extracts were washed with water (20 mL), brine (2×20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel (0-50% EtOAc/heptanes)

Sources & evidence

ORD record
ord-10d1fb3efbc942d199237fe2e3740e23
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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