4-Fluoroaniline → HCID 44242246, compound

HRID 2198305Notes

Reaction equation

HRID 2198305 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([OH:14])=O)[C:6]1[CH2:15][N:16]([CH3:19])[CH2:17][CH2:18][C:5]2=1.C(Cl)(=O)C(Cl)=O.[F:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1>ClCCl.CN(C)C=O.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([NH:31][C:30]1[CH:32]=[CH:33][C:27]([F:26])=[CH:28][CH:29]=1)=[O:14])[C:6]1[CH2:15][N:16]([CH3:19])[CH2:17][CH2:18][C:5]2=1

Participants

7

Reactant 3

HCID 97314-FluoroanilineHCID 65578Oxalyl chlorideHCID 44242581HCID 44242581, compound

Product 1

HCID 44242246HCID 44242246, compoundYield 4.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(6-chloro-1,2,3,4-tetrahydro-2-methylpyrido[3,4-b]indol-9-yl)acetic acid (0.1 g, 0.39 mmol) was dissolved in dichloromethane (4 mL) and was cooled to 0° C., using an ice-bath; oxalyl chloride (0.04 mL, 0.43 mmol) was added drop-wise to the reaction mixture. Catalytic amount (1 drop) of dimethyl formamide was added and the reaction mixture was stirred for 1 h at room temperature. Excess oxalyl chloride was distilled away under reduced pressure. A solution of 4-fluoroaniline (0.042 g, 0.43 mmol) in dichloromethane (2 mL) and 4-dimethylaminopyridine (0.017 g, 0.143 mmol) was added to the residue under nitrogen at room temperature and the reaction mass was stirred for 30 min. The reaction mixture was quenched with water and neutralized with 10% NaHCO3, extracted with dichloromethane (2×10 mL). The combined organic layer was dried over sodium sulfate and concentrated by rotary evaporation to obtain 2-(6-chloro-1,2,3,4-tetrahydro-2-methylpyrido[3,4-b]indol-9-yl)-N-(4-fluorophenyl)acetamide (6 mg) after purification by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection volume 5 mL). 1 H NMR (DMSO): 11.4 (s, 1H), 10.6 (s, 1H), 7.6 (m, 3H), 7.4 (d, 1H), 7.3-7.1 (m, 3H), 5.1 and 4.9 (d, 2H), 4.4 (q, 2H), 4.1-3.9 (bs, 2H), 3.5 (s, 3H), 3.2-3.1 (m, 2H).

Workup

  1. distillationExcess oxalyl chloride was distilled away under reduced pressure
  2. stirringthe reaction mass was stirred for 30 min
  3. customThe reaction mixture was quenched with water and neutralized with 10% NaHCO3
  4. extractionextracted with dichloromethane (2×10 mL)
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-e62c3cbbb31947808162c02625830220
Source dataset
uspto-grants-2012_12
Patent number
US08338447B2

Reaction notes

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