2-Methyl-2-butene → 5-{4-[2-(acetylamino)ethoxy]phenyl}-6-chloro-1H-indole-3-carboxylic acid

HRID 1054589Notes

Reaction equation

HRID 1054589 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:25]=[CH:24][C:16]([O:17][CH2:18][CH2:19][NH:20][C:21](=[O:23])[CH3:22])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:32].[Na+].OP([O-])(O)=O.[Na+]>C(#N)C.O.C(O)(C)(C)C>[C:21]([NH:20][CH2:19][CH2:18][O:17][C:16]1[CH:24]=[CH:25][C:13]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[NH:8][CH:7]=[C:6]3[C:11]([OH:32])=[O:12])=[CH:14][CH:15]=1)(=[O:23])[CH3:22]

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86698590N-{2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]ethyl}acetamide

Product 1

HCID 866985915-{4-[2-(acetylamino)ethoxy]phenyl}-6-chloro-1H-indole-3-carboxylic acidYield 26%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-{2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]ethyl}acetamide (80 mg, 0.23 mmol) in acetonitrile (3 mL) was added tert-butanol (3 mL) and 2-methyl-2-butene (1.89 mL). The reaction mixture was cooled to 0° C., and treated with a solution of sodium chlorite (452 mg, 6.74 mmol) and sodium phosphate monobasic (930 g, 6.74 mmol) in water (3 mL) dropwise. The reaction mixture was stirred at room temperature for 40 h. The reaction mixture was quenched with sodium sulfite and concentrated in vacuo to give a solid. The crude product was washed with DMF and the filtrate was concentrated in vacuo to give a brown residue, which was purified by prep-HPLC to give 5-{4-[2-(acetylamino)ethoxy]phenyl}-6-chloro-1H-indole-3-carboxylic acid (22 mg, 26%) as an off-white solid. MS (ES+) 373.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.93 (s, 1 H), 8.14 (br. s., 1 H), 8.06 (s, 1 H), 7.93 (s, 1 H), 7.62 (s, 1 H), 7.34 (d, 2 H), 7.02 (d, 2 H), 4.03 (t, 2 H), 3.45-3.43 (m, 2 H), 1.84 (s, 3 H).

Workup

  1. customThe reaction mixture was quenched with sodium sulfite
  2. concentrationconcentrated in vacuo
  3. customto give a solid
  4. washThe crude product was washed with DMF
  5. concentrationthe filtrate was concentrated in vacuo
  6. customto give a brown residue, which
  7. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-6457c9cd9e1048ea8d7022467e476e6a
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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