Oxalyl chloride → 6-chloro-4-(3-hydroxyphenyl)-3-(3-methyl-isoxazol-5-yl)-1H-quinolin-2-one

HRID 2053423Notes

Reaction equation

HRID 2053423 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[CH:7]=1)=O.[CH3:18][C:19]1[CH:23]=[C:22]([CH2:24][C:25](Cl)=[O:26])[O:21][N:20]=1.Cl.CC1C=C(CC(O)=O)ON=1.C(Cl)(=O)C(Cl)=O>C(Cl)Cl.C(N(CC)CC)C.CN(C)C=O>[Cl:17][C:14]1[CH:13]=[C:3]2[C:2](=[CH:16][CH:15]=1)[NH:1][C:25](=[O:26])[C:24]([C:22]1[O:21][N:20]=[C:19]([CH3:18])[CH:23]=1)=[C:4]2[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[CH:7]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 2794900(2-Amino-5-chlorophenyl)(3-hydroxyphenyl)methanoneHCID 123668732-(3-Methylisoxazol-5-yl)acetyl chlorideHCID 67010666HCID 67010666, compound

Product 1

HCID 1354970676-chloro-4-(3-hydroxyphenyl)-3-(3-methyl-isoxazol-5-yl)-1H-quinolin-2-oneYield 70.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A mixture of 2-amino-5-chloro-3′-hydroxybenzophenone (0.1 g, 0.4 mmol), (3-methyl-isoxazol-5-yl)-acetyl chloride (1.18 mmol) [synthesized from the reaction between (3-methyl-isoxazol-5-yl)-acetic acid hydrochloride and oxalyl chloride catalyzed by N,N-dimethylformamide in DCM], triethylamine (Et3N) (0.20 mL) and DCM (10 mL) was heated to reflux overnight. The mixture was then cooled to room temperature and concentrated, and the residue was purified by flash chromatography on silica gel (5% methanol in DCM) to give 6-chloro-4-(3-hydroxyphenyl)-3-(3-methyl-isoxazol-5-yl)-1H-quinolin-2-one (99 mg, 70%). 1H NMR (300 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.68-7.60 (m, 2H), 7.43 (d, J=10.0 Hz, 1H), 7.25 (t, J=10.0 Hz, 1H), 7.01-6.97 (m, 1H), 6.88-6.80 (m, 1H), 6.68-6.59 (m, 1H), 6.47 (s, 1H), 2.15 (s, 3H). MS: 353.2 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated
  4. customthe residue was purified by flash chromatography on silica gel (5% methanol in DCM)

Sources & evidence

ORD record
ord-c15a2c0a8f134028be82db83641f9d26
Source dataset
uspto-grants-2008_02
Patent number
US07326788B2

Reaction notes

Loading…