Potassium Phosphate, Tribasic → 4-[4-Fluoro-2-methoxy-5-(methylsulfonylmethyl)phenyl]-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one

HRID 575584Notes

Reaction equation

HRID 575584 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5]([F:13])=[CH:4][C:3]=1[O:14][CH3:15].[CH3:16][N:17]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:36]3[CH:37]=[N:38][N:39]([CH3:41])[CH:40]=3)[CH:23]=2)[C:18]1=[O:42].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:13][C:5]1[C:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:7][C:2]([C:25]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:36]4[CH:37]=[N:38][N:39]([CH3:41])[CH:40]=4)[CH:23]=3)[C:18](=[O:42])[N:17]([CH3:16])[CH:26]=2)=[C:3]([O:14][CH3:15])[CH:4]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180225411-Bromo-4-fluoro-2-methoxy-5-(methylsulfonylmethyl)benzeneHCID 1237513492-Methyl-6-(1-methylpyrazol-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one

Product 1

HCID 1180216194-[4-Fluoro-2-methoxy-5-(methylsulfonylmethyl)phenyl]-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-oneYield 19.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

1-Bromo-4-fluoro-2-methoxy-5-(methylsulfonylmethyl)benzene (34.0 mg, 0.114 mmol), the title compound of Example 46, step 2 (50.0 mg, 0.137 mmol), Pd(dppf)Cl2 (20.0 mg, 0.027 mmol) and 1 M aqueous K3PO4 (0.47 mL, 0.47 mmol) in dioxane (3.0 mL) were microwaved at 100° C. for 40 min. Preparative HPLC gave the title compound (10.0 mg, 18%) as a light yellow solid. 1H NMR: (CDCl3, 400 MHz) δ 8.47 (d, J=8.0 Hz, 1H), 7.74 (s, 1H), 7.73 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.42 (d, J=8.4 Hz, 1H), 7.27 (s, 1H), 7.05 (s, 1H), 6.85 (d, J=12.0 Hz, 1H), 4.32 (d, J=6.4 Hz, 2H), 3.93 (s, 3H), 3.77 (s, 3H), 3.64 (s, 3H), 2.93 (s, 3H). LCMS: 456.1 (M+H)+.

Sources & evidence

ORD record
ord-5790adb35d964caaace753548006fd7f
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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