1H-indole-6-carbonitrile → HCID 69200222, compound

HRID 2220669Notes

Reaction equation

HRID 2220669 reaction equation
[C:1]([O:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[C:22]3[C:17](=[CH:18][C:19]([C:23]#[N:24])=[CH:20][CH:21]=3)[N:16](CC)[CH:15]=2)=[C:9]([Br:27])[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C[NH-].C(C1C=C2C(C=CN2)=CC=1)#N.CC(C)([O-:45])C.[K+]>C(O)(C)(C)C.C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([CH:13]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([C:23]#[N:24])=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[OH:45])=[C:9]([Br:27])[CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 851461H-indole-6-carbonitrileHCID 21952893MethylamideHCID 23665647Potassium tert-butoxideHCID 69199920HCID 69199920, compound

Product 1

HCID 69200222HCID 69200222, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Part A. 3-bromo-4-(6-cyano-1-ethyl-1H-indol-3-ylmethyl)-benzoic acid tert-butyl ester: A mixture of the compound of Example 10, Part A (5 g, 0.175 mol) and 6-cyanoindole (1.7 g, 0.0.12 mol) in t-butanol (60 ml) and THF (˜5 mL) was treated with potassium t-butoxide (0.012 mol) and the mixture was stirred at rt under N2. After 18 h the reaction mixture was diluted with EtOAc and washed with water and brine, dried over anh. Na2SO4, filtered and solvent evaporated. The residue was purified by flash chromatography on silica gel to provide 3-Bromo-4-[(6-cyano-1H-indol-3-yl)-hydroxy-methyl]-benzoic acid tert-butyl ester (4.05 g, 79%) as an off-white foam. 1H NMR (400 MHz, CDCl3) δ ppm 1.58 (s, 9H) 2.43 (d, J=0.39 Hz, 1H) 6.47 (d, J=0.39 Hz, 1H) 7.11 (d, J=2.20 Hz, 1H) 7.36 (d, J=8.35 Hz, 1H) 7.70 (s, 1H) 7.78 (dd, J=15.60, 8.13 Hz, 2H) 7.98 (m, 1H) 8.14 (s, 1H) 8.39 (s, 1H). This material was dissolved in methylene chloride (55 ml) and cooled in an ice/salt water bath under N2. To the cold, stirred solution was added triethylsilane (3.03 mL, 2 eq) followed by slow addition of trifluoroacetic acid (0.72 mL, 1 eq) over 20-25 min. The resulting solution was stirred for 1 h allowing ice bath to melt and reaction to gradually assume rt. Additional methylene chloride was added and the solution was washed with brine, dried and evaporated.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anh. Na2SO4
  3. filtrationfiltered
  4. customsolvent evaporated
  5. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-413627cb04114ba9a723a242a89b00cd
Source dataset
uspto-grants-2008_08
Patent number
US07417063B2

Reaction notes

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