Triethylamine → HCID 118341170, compound

HRID 925640Notes

Reaction equation

HRID 925640 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[C:13](I)=[CH:12][C:11]([C:15]#[N:16])=[CH:10][C:9]=1[Br:17])([CH3:4])([CH3:3])[CH3:2].[CH2:19]([O:21][CH:22]([O:25][CH2:26][CH3:27])[C:23]#[CH:24])[CH3:20].C(N(CC)CC)C.N1CCCN2CCCCCC=12>[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O.CN(C=O)C>[C:1]([O:5][C:6]([N:7]1[C:8]2[C:13](=[CH:12][C:11]([C:15]#[N:16])=[CH:10][C:9]=2[Br:17])[CH:24]=[C:23]1[CH:22]([O:25][CH2:26][CH3:27])[O:21][CH2:19][CH3:20])=[O:18])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 662853,3-DiethoxypropyneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 90035981HCID 90035981, compound

Product 1

HCID 118341170HCID 118341170, compoundYield 69.9%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (2-bromo-4-cyano-6-iodo-phenyl)-carbamic acid tert-butyl ester (step A) (413 mg, 0.98 mmol), 3,3-diethoxyprop-1-yne (125 mg, 140 μl, 0.98 mmol), triethylamine (395 mg, 544 μl, 3.9 mmol), copper(I)iodide (5.58 mg, 29.3 μmol) and bis(triphenylphosphine)-palladium(II)chloride (34.3 mg, 48.8 μmol) was allowed to stir for 3 h at room temperature. Afterwards 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (297 mg, 292 μl, 1.95 mmol) and DMF (1.58 ml) were added, and the reaction mixture was allowed to stir for 17 h at room temperature, poured into water (10 ml) and extracted with ethyl acetate (2×20 ml). The combined organic layers were washed with brine, dried (MgSO4) and evaporated. The crude product (0.51 g) was further purified by flash chromatography on silica gel (heptane/ethyl acetate 0-20%) to yield 7-bromo-5-cyano-2-diethoxymethyl-indole-1-carboxylic acid tert-butyl ester (0.29 g, 64%) as a light yellow oil, MS (EI) m/z=422 [(M)+].

Workup

  1. stirringto stir for 17 h at room temperature
  2. extractionextracted with ethyl acetate (2×20 ml)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product (0.51 g) was further purified by flash chromatography on silica gel (heptane/ethyl acetate 0-20%)

Sources & evidence

ORD record
ord-8fd57b1d53a34e17897a85cfea58bf12
Source dataset
uspto-grants-2016_03
Patent number
US09284321B2

Reaction notes

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