3-Methoxypropyne → 4-(3-Methoxy-1-propinyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone

HRID 21224

Reaction equation

HRID 21224 reaction equation
FC(F)(F)S(O[C:7]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:20][CH:19]=3)=[C:12]2[C:8]=1[CH2:9][NH:10][C:11]2=[O:39])(=O)=O.[CH2:42]([O:45][CH3:46])[C:43]#[CH:44]>C(NCC)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)I>[CH3:46][O:45][CH2:42][C:43]#[C:44][C:7]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]([C:32]([O:34][C:35]([CH3:38])([CH3:36])[CH3:37])=[O:33])[C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([CH2:25][N:26]2[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)=[CH:20][CH:19]=3)=[C:12]2[C:8]=1[CH2:9][NH:10][C:11]2=[O:39]

Participants

6

Reactant 2

HCID 693933-MethoxypropyneHCID 866282864-Trifluoromethanesulfonyloxy-7-(1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone

Product 1

HCID 1317282364-(3-Methoxy-1-propinyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinoneYield 72.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

In a similar manner to Step 2 of Example 161, 4-trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (400 mg, 0.674 mmol) was dissolved in diethylamine (16 mL), and the solution was treated with bis(triphenylphosphine)dichloropalladium (56.7 mg, 0.012 mmol), copper iodide (46.2 mg, 0.243 mmol) and methyl propargyl ether (0.398 mL, 4.72 mmol), followed by purification by preparative thin-layer chromatography (chloroform/methanol=6/1 to 8/1) to obtain 4-(3-methoxy-1-propinyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (250 mg, yield 72%).

Workup

  1. customfollowed by purification by preparative thin-layer chromatography (chloroform/methanol=6/1 to 8/1)

Sources & evidence

ORD record
ord-9535bcdb52f54ffd9cf5f6efa6533d76
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

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