p-Toluenesulfonic acid → HCID 86728243, compound

HRID 1776837Notes

Reaction equation

HRID 1776837 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([OH:18])=[CH:4][CH:3]=1.[S:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[CH:24]=O.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:24]([C:20]3[S:19][CH:23]=[CH:22][CH:21]=3)[C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][C:14]=4[F:17])[NH:9][C:8]=3[C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 73642-ThiophenecarboxaldehydeHCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

Product 1

HCID 86728243HCID 86728243, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of compound 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (60 mg, 0.224 mmol), thiophene-2-carbaldehyde (50 mg, 0.448 mmol) and PTSA (85 mg, 0.448 mmol) in toluene (1 mL) was stirred at 60° C. for 4 hours. The mixture was then diluted with water (20 mL) and extracted with EtOAc (15 mL*3). The organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether:EtOAc=20:1) to provide 2-chloro-7-fluoro-6-(thiophen-2-yl)-6,11-dihydropyrido[2′,3′:5,6]pyrano[4,3-b]indole (40 mg, yield: 50.0%). 1H-NMR (CDCl3, 400 MHz) δ 9.28 (s, 1H), 7.07˜7.18 (m, 5H), 6.98 (d, J=8.4 Hz, 1H), 6.81˜6.86 (m, 2H), 6.66˜6.70 (m, 1H). MS (M+H)+: 357/359.

Workup

  1. extractionextracted with EtOAc (15 mL*3)
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified

Sources & evidence

ORD record
ord-cac64b172bac42689b30e97de83fa791
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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