1-Ethynyl-4-(methanesulfonyl)benzene → (4-{3-[3-(4-Methanesulfonyl-phenylethynyl)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester

HRID 548568Notes

Reaction equation

HRID 548568 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][CH:4]=1)#[CH:2].[CH3:13][O:14][C:15](=[O:45])[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]#[C:27][C:28]2[CH:33]=[C:32]([C:34]#[C:35][CH2:36][N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[CH:31]=[C:30](Br)[CH:29]=2)=[CH:20][C:19]=1[CH3:44]>CN(C=O)C.C(N(CC)CC)C.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.[Cu]I>[CH3:13][O:14][C:15](=[O:45])[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]#[C:27][C:28]2[CH:33]=[C:32]([C:34]#[C:35][CH2:36][N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[CH:31]=[C:30]([C:2]#[C:1][C:3]3[CH:4]=[CH:5][C:6]([S:9]([CH3:12])(=[O:10])=[O:11])=[CH:7][CH:8]=3)[CH:29]=2)=[CH:20][C:19]=1[CH3:44]

Participants

7

Reactant 2

HCID 220426121-Ethynyl-4-(methanesulfonyl)benzeneHCID 67157848(4-{3-[3-Bromo-5-(3-morpholin-4-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methylphenoxy)-acetic acid methyl ester

Product 1

HCID 67158555(4-{3-[3-(4-Methanesulfonyl-phenylethynyl)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 1-ethynyl-4-methanesulfonyl-benzene (346 mg, 1.92 mmol), (4-{3-[3-bromo-5-(3-morpholin-4-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester (123 mg, 0.24 mmol, example 6), Pd(PPh3)2Cl2 (17 mg, 0.024 mmol), CuI (12 mg, 0.067 mmol) in dry DMF (2 ml) and triethylamine (2 ml) was heated in a microwave own for 1 hour at 65° C. in a sealed tube. The reaction mixture was filtered through Decalite and the filtrate was evaporated. The residue was purified on column chromatography using methylene chloride/THF mixtures to give (4-{3-[3-(4-methanesulfonyl-phenylethynyl)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester in 50 mg (34%) yield.

Workup

  1. filtrationThe reaction mixture was filtered through Decalite
  2. customthe filtrate was evaporated
  3. customThe residue was purified on column chromatography

Sources & evidence

ORD record
ord-9f5ead2f54464d9a96c0c106400c7465
Source dataset
uspto-grants-2011_05
Patent number
US07943612B2

Reaction notes

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