Sodium hydride → HCID 58561015, compound

HRID 2408153Notes

Reaction equation

HRID 2408153 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([CH3:14])[CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[OH:15].Br[C@H:17]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=1)[C@@H:18]([C:22]1[CH:34]=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:24][CH:23]=1)[CH2:19][CH2:20][CH3:21]>CN(C=O)C.CCOC(C)=O.O>[Cl:3][C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([CH3:14])[CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[O:15][C@@H:17]([C:35]1[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=1)[C@@H:18]([C:22]1[CH:34]=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])=[CH:24][CH:23]=1)[CH2:19][CH2:20][CH3:21]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 58561017HCID 58561017, compoundHCID 178426082HCID 178426082, compound

Product 1

HCID 58561015HCID 58561015, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Sodium hydride (60 wt % in mineral oil, 15.5 mg, 0.387 mmol) was washed with hexanes (2 mL), then a solution of 6-chloro-8-methylquinolin-4-ol (50.0 mg, 0.258 mmol) in DMF (2 mL) was added. Once gas evolution had ceased, the product of Step A (170 mg, 0.387 mmol) was added in one portion, then the mixture was stirred at 120° C. overnight. After being allowed to cool to room temperature, the mixture was diluted with EtOAc (20 mL) and water (15 mL), then the organic layer was concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to afford the title compound. 1H NMR (500 MHz, CDCl3): δ 8.51 (d, J=5 Hz, 1H); 7.93 (d, J=8.5 Hz, 2H); 7.89 (d, J=2.5 Hz, 1H); 7.47 (s, 1H); 7.26 (dd, J=6.5, 6.0 Hz, 4H); 7.12 (d, J=8.5 Hz, 2H); 6.43 (d, J=5 Hz, 1H); 5.44 (d, J=6.5 Hz, 1H); 3.29-3.23 (m, 1H); 2.69 (s, 3H); 1.90-1.80 (m, 1H); 1.74-1.64 (m, 1H); 1.58 (s, 9H); 1.30-1.10 (m, 2H); 0.83 (t, J=7.5 Hz, 3H); LC4 2.78 min. (M+H)+ 550.

Workup

  1. temperatureto cool to room temperature
  2. concentrationthe organic layer was concentrated
  3. customThe resulting residue was purified by silica gel chromatography
  4. washeluting with 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-7cea27b0e4264b1eb940559c06c844b4
Source dataset
uspto-grants-2014_08
Patent number
US08809579B2

Reaction notes

Loading…