Methanol → HCID 51347782, compound

HRID 2370986Notes

Reaction equation

HRID 2370986 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:24]#[N:25])[C:9]3[C:14]([C:15]=2[C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[CH:18][CH:17]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:26])[O:4][N:3]=1.B(Br)(Br)Br.CO.O>C(Cl)Cl>[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:24]#[N:25])[C:9]3[C:14]([C:15]=2[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:26])[O:4][N:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 25134Boron tribromideHCID 67109260HCID 67109260, compound

Product 1

HCID 51347782HCID 51347782, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-50 °C

Procedure

2-(3,5-dimethylisoxazol-4-yl)-3-(4-methoxyphenyl)-1H-indole-1-carbonitrile was dissolved in 3 ml DCM and the mixture was cooled to −50° C. BBr3 (5 eq) was added and the reaction was stirred at −50° C. for 4.5 h and then at −20° C. for 16 h. The mixture was cooled to −78° C. and MeOH (90 μl) was added followed by water. The aqueous layer was extracted with DCM 3× and the combined organic layers were concentrated. The crude product was purified on silica (EtOAc/n-Heptane 2:8-3:7). 4.9 mg 2-(3,5-dimethylisoxazol-4-yl)-3-(4-hydroxyphenyl)-1H-indole-1-carbonitrile was obtained as a white solid. ES/MS m/z: 330.2 (M+H), 328.3 (M−H); 1H NMR (CDCl3, 500 MHz): 7.75 (m, 1H), 7.67 (m, 1H), 7.51 (m, 1H), 7.41 (m, 1H), 7.20 (m, 2H), 6.88 (m, 2H), 2.28 (s, 3H) and 2.05 (s, 3H).

Workup

  1. waitat −20° C. for 16 h
  2. temperatureThe mixture was cooled to −78° C.
  3. extractionThe aqueous layer was extracted with DCM 3×
  4. concentrationthe combined organic layers were concentrated
  5. customThe crude product was purified on silica (EtOAc/n-Heptane 2:8-3:7)

Sources & evidence

ORD record
ord-830bec240bf34dd18c0e363c17005d42
Source dataset
uspto-grants-2014_04
Patent number
US08710243B2

Reaction notes

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