Sodium Iodide → (S)-7-chloro-4-[2,2-difluoro-2-(1-methylpiperidin-2-yl)-ethoxy]-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide

HRID 1858111Notes

Reaction equation

HRID 1858111 reaction equation
Cl[CH2:2][C:3]([C@@H:6]1[CH2:11][CH2:10][CH2:9][CH2:8][N:7]1[CH3:12])([F:5])[F:4].[N:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][C:31]=2[Cl:32])[NH:28][C:27](=[O:33])[C:26]([C:34]2[CH:39]=[C:38]([CH3:40])[CH:37]=[C:36]([CH3:41])[CH:35]=2)=[C:25]3[OH:42])=[O:21])=[N:15][CH:14]=1.C(=O)(O)[O-].[K+].[I-].[Na+]>>[N:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][C:31]=2[Cl:32])[NH:28][C:27](=[O:33])[C:26]([C:34]2[CH:35]=[C:36]([CH3:41])[CH:37]=[C:38]([CH3:40])[CH:39]=2)=[C:25]3[O:42][CH2:2][C:3]([F:5])([F:4])[C@@H:6]2[CH2:11][CH2:10][CH2:9][CH2:8][N:7]2[CH3:12])=[O:21])=[N:15][CH:14]=1

Participants

5

Reactant 4

HCID 5238Sodium IodideHCID 516893Potassium BicarbonateHCID 54031855(S)-2-(2-chloro-1,1-difluoroethyl)-1-methylpiperidineHCID 547300977-Chloro-3-(3,5-dimethylphenyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide

Product 1

HCID 53888319(S)-7-chloro-4-[2,2-difluoro-2-(1-methylpiperidin-2-yl)-ethoxy]-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamideYield 63.3%

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-2-(2-chloro-1,1-difluoroethyl)-1-methylpiperidine (39 mg in 1.5 mL N,N-dimethylformamide) was added 7-chloro-3-(3,5-dimethylphenyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (64 mg), potassium bicarbonate (32 mg) and sodium iodide (25 mg) then heated to 80° C. on an oil bath. After 16 hours, the reaction was cooled to room temperature and concentrated in vacuo. Purification of the crude product by preparative tic on silica gel (chloroform:2M ammonium in methanol, 97:3) gave the title compound (56 mg). MASS: 582 (M+H)

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customPurification of the crude product by preparative tic on silica gel (chloroform:2M ammonium in methanol, 97:3)

Sources & evidence

ORD record
ord-ccbcdd5c7b5242dcbac1f4636cd0a00f
Source dataset
uspto-grants-2000_11
Patent number
US06150352

Reaction notes

Loading…