Dimethylformamide → [4-(3-cyclopropylethynyl-1-cyclopropylmethyl-6-ethoxy-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl ester

HRID 502276Notes

Reaction equation

HRID 502276 reaction equation
[CH:1]([O:4][C:5](=[O:30])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([CH2:26][CH:27]3[CH2:29][CH2:28]3)[C:15]3[C:20]([C:21]=2I)=[CH:19][CH:18]=[C:17]([O:23][CH2:24][CH3:25])[CH:16]=3)=[CH:9][CH:8]=1)([CH3:3])[CH3:2].[CH:31]1([C:34]#[CH:35])[CH2:33][CH2:32]1.C(N(CC)CC)C.CN(C=O)C>CCOC(C)=O.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>[CH:1]([O:4][C:5](=[O:30])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([CH2:26][CH:27]3[CH2:29][CH2:28]3)[C:15]3[C:20]([C:21]=2[C:35]#[C:34][CH:31]2[CH2:33][CH2:32]2)=[CH:19][CH:18]=[C:17]([O:23][CH2:24][CH3:25])[CH:16]=3)=[CH:9][CH:8]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 138823Cyclopropylacetylene2×HCID 59425548[4-(1-cyclopropylmethyl-6-ethoxy-3-iodo-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl ester

Product 1

HCID 59425623[4-(3-cyclopropylethynyl-1-cyclopropylmethyl-6-ethoxy-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl esterYield 24.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

[4-(1-Cyclopropylmethyl-6-ethoxy-3-iodo-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl ester (100 mg, 0.19 mmol), cyclopropylacetylene (50 μL, 70% in toluene, 0.4 mmol), Pd(PPh3)2Cl2 (6.7 mg, 0.0096 mmol), CuI (5 mg, 0.026 mmol), triethylamine (600 μL), and DMF (600 μL) was stirred at room temperature for 5 h. Additional Pd(PPh3)2Cl2 (5 mg), and cyclopropylacetylene (30 μL) was then added and the reaction mixture was stirred overnight. The reaction mixture was diluted with EtOAc and washed with H2O and aq. HCl. The organic layer was dried, concentrated and purified by silica gel chromatography (3:1 CH2Cl2/hexane), followed by a second chromatography (7:3 hexane/ether) to provide [4-(3-cyclopropylethynyl-1-cyclopropylmethyl-6-ethoxy-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl ester (21 mg, 24%) as a white solid.

Workup

  1. washwashed with H2O and aq. HCl
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. custompurified by silica gel chromatography (3:1 CH2Cl2/hexane)

Sources & evidence

ORD record
ord-7f9186fb4f2c41efb032eee02c3da55f
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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