Nitrogen → 4-[5-Amino-2-(2,4-difluorophenoxy)phenyl]-2-methyl-2,7-naphthyridin-1-one

HRID 575559Notes

Reaction equation

HRID 575559 reaction equation
N#N.[F:3][C:4]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:5]=1[O:6][C:7]1[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][C:8]=1B1OC(C)(C)C(C)(C)O1.Br[C:29]1[C:38]2[C:33](=[CH:34][N:35]=[CH:36][CH:37]=2)[C:32](=[O:39])[N:31]([CH3:40])[CH:30]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[NH2:11][C:10]1[CH:12]=[CH:13][C:7]([O:6][C:5]2[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:4]=2[F:3])=[C:8]([C:29]2[C:38]3[C:33](=[CH:34][N:35]=[CH:36][CH:37]=3)[C:32](=[O:39])[N:31]([CH3:40])[CH:30]=2)[CH:9]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 896576134-(2,4-Difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 1180220834-Bromo-2-methyl-1,2-dihydro-2,7-naphthyridin-1-one

Product 1

HCID 1180217274-[5-Amino-2-(2,4-difluorophenoxy)phenyl]-2-methyl-2,7-naphthyridin-1-oneYield 53.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

For 5 min, N2 was bubbled through a mixture of 4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (64.8 mg, 0.187 mmol), the title compound of Example 51, step 2 (30.0 mg, 0.124 mmol), K2CO3 (51.6 mg, 0.374 mmol) and Pd(dppf)Cl2 (18.3 mg, 0.025 mmol) in dioxane (2.0 mL) and water (0.2 mL) which was then microwaved at 100° C. for 1 h. Purification by preparative TLC (DCM:MeOH=20:1, Rf=0.5) gave the title compound (25.0 mg, 53%) as yellow gum. LCMS: 380.0 (M+H)+

Workup

  1. customPurification by preparative TLC (DCM:MeOH=20:1, Rf=0.5)

Sources & evidence

ORD record
ord-2f7095a51b5b40728ed8c39bc8d2e76a
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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