Methanol → 6-(benzylthio)-1-(4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)-3-methoxyquinolin-2(1H)-one

HRID 1504455Notes

Reaction equation

HRID 1504455 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[CH:11][C:12]([NH:17][C:18]2[C:23]([O:24][CH3:25])=[CH:22][C:21]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([CH3:33])[CH:27]=3)=[C:20]([F:34])[CH:19]=2)=[C:13]([CH:16]=1)[CH:14]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C[O-].[Na+].C[O:41][CH2:42][C:43]([O:45][CH3:46])=O>C(Cl)Cl.CCOC(C)=O.C1(C)C=CC=CC=1>[CH2:1]([S:8][C:9]1[CH:16]=[C:13]2[C:12](=[CH:11][CH:10]=1)[N:17]([C:18]1[C:23]([O:24][CH3:25])=[CH:22][C:21]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([CH3:33])[CH:27]=3)=[C:20]([F:34])[CH:19]=1)[C:42](=[O:41])[C:43]([O:45][CH3:46])=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 80507Methyl methoxyacetateHCID 10942334Sodium MethoxideHCID 1177373105-(Benzylthio)-2-((4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)amino)benzaldehyde

Product 1

HCID 1177371086-(benzylthio)-1-(4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)-3-methoxyquinolin-2(1H)-oneYield 45.7%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
70 °C

Procedure

A flask was charged with 5-(benzylthio)-2-((4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)amino)benzaldehyde (0.809 g, 1.644 mmol) and a MeOH solution of sodium methoxide (16.44 ml, 8.22 mmol) was added. Then methyl methoxyacetate (0.489 ml, 4.93 mmol) followed by toluene (1.644 ml) were added. A reflux condenser was attached and the mixture was heated at 70° C. for 48 h. The resulting solution was concentrated for purification by MPLC (Biotage Isolera). The crude residue was taken up in minimal DCM and absorbed onto a 25 g loading cartridge and passed through a Redi-Sep® Gold pre-packed silica gel column (40 g) using 95:5 Heptane: EtOAc to 100% EtOAc gradient (with 1% DCM for solubility) to afford 6-(benzylthio)-1-(4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)-3-methoxyquinolin-2(1H)-one (0.410 g, 0.751 mmol, 45.7% yield) as a off-white amorphous solid. (ESI) 546.0 (M+H)+.

Workup

  1. additionwere added
  2. customA reflux condenser was attached
  3. concentrationThe resulting solution was concentrated for purification by MPLC (Biotage Isolera)
  4. customabsorbed onto a 25 g loading cartridge

Sources & evidence

ORD record
ord-bd7be8cce0a14b88ac851228683f28ee
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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