Triethylamine → 2-(6-{3-[(1-Methylpiperidin-4-yloxy)-pyridin-2-ylmethyl]phenyl}hex-5-ynyl)isoindole-1,3-dione

HRID 593381Notes

Reaction equation

HRID 593381 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:23]([N:29]1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39])[CH2:24][CH2:25][CH2:26][C:27]#[CH:28].C(N(CC)CC)C>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.CN1CCCC1=O>[CH3:22][N:19]1[CH2:20][CH2:21][CH:16]([O:15][CH:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[C:4]2[CH:3]=[C:2]([C:28]#[C:27][CH2:26][CH2:25][CH2:24][CH2:23][N:29]3[C:33](=[O:34])[C:32]4[C:31](=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:30]3=[O:39])[CH:7]=[CH:6][CH:5]=2)[CH2:17][CH2:18]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 3346053N-(5-Hexynyl)phthalimideHCID 726947252-[(3-Iodophenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine

Product 1

HCID 867038712-(6-{3-[(1-Methylpiperidin-4-yloxy)-pyridin-2-ylmethyl]phenyl}hex-5-ynyl)isoindole-1,3-dione

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

A screw-cap tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine (105 mg, example 37), tetrakis(triphenylphosphine)palladium (52 mg), copper(I) iodide (26 mg), N-5-hexynylphthalimide (186 mg), triethylamine (400 μL) and 1-methyl-2-pyrrolidinone (4 mL). The tube is evacuated, filled with argon and sealed. After stirring at 90° C. for 14 h, the mixture is diluted with water and the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5) to give 2-(6-{3-[(1-methylpiperidin-4-yloxy)-pyridin-2-ylmethyl]phenyl}hex-5-ynyl)isoindole-1,3-dione as an brown oil.

Workup

  1. customThe tube is evacuated
  2. additionfilled with argon
  3. customsealed
  4. additionthe mixture is diluted with water
  5. extractionthe aqueous phase is extracted with ethyl acetate
  6. washThe pooled organic extracts are washed with water
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)

Sources & evidence

ORD record
ord-13f67e5db34b494785dc05860f9d275d
Source dataset
uspto-grants-2016_01
Patent number
US09242959B2

Reaction notes

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