Potassium Phosphate, Tribasic → 4-(5-Amino-2-fluorophenyl)-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one

HRID 575549Notes

Reaction equation

HRID 575549 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)[CH:10]=2)[C:5](=[O:18])[N:4]([CH3:19])[CH:3]=1.[F:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][C:22]=1B1OC(C)(C)C(C)(C)O1.[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]>[NH2:25][C:24]1[CH:23]=[CH:22][C:21]([F:20])=[C:27]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:12]4[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=4)[CH:10]=3)[C:5](=[O:18])[N:4]([CH3:19])[CH:3]=2)[CH:26]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 722211464-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)anilineHCID 1180215864-Bromo-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one

Product 1

HCID 1180221374-(5-Amino-2-fluorophenyl)-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-oneYield 64%

Reagents, catalysts & solvents 2

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

Procedure

4-Bromo-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one (35 mg, 0.11 mmol), 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (29 mg, 0.12 mmol), Pd(dppf)Cl2 (8 mg, 0.01 mmol) and aqueous 1 M K3PO4 (0.3 mL) in dioxane (1.2 mL) were microwaved at 120° C. for 1.25 h. Work up was similar to that described for Example 18, step 3. Silica gel chromatography, eluting with 100% EA followed by 10% methanol in EA, gave the title compound (25 mg, 0.07 mmol) as a cream solid in 64% yield. LCMS (M+H)+ 349.

Workup

  1. washSilica gel chromatography, eluting with 100% EA

Sources & evidence

ORD record
ord-4f04a3973d7f4012a29c891b57ddca7d
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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