Ethyl Acetate → 5-(7-Chloro-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylaniline

HRID 715096Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8]([CH3:18])=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][N:13]=[C:12]([Cl:17])[CH:11]=2)(=O)=O.[F:21][C:22]1[CH:28]=[C:27]([CH3:29])[C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][C:23]=1[NH2:24].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:17][C:12]1[CH:11]=[C:10]2[C:15]([CH:16]=[C:7]([C:26]3[C:27]([CH3:29])=[CH:28][C:22]([F:21])=[C:23]([CH:25]=3)[NH2:24])[C:8]([CH3:18])=[N:9]2)=[CH:14][N:13]=1

Participants

Conditions

Temperature: 60 °C

Procedure

Sparge a mixture of 7-chloro-2-methyl-1,6-naphthyridin-3-yl trifluoromethanesulfonate (2.250 g, 6.89 mmol) and 2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.729 g, 6.89 mmol) in dioxane (32 mL) with argon, add a solution of K2CO3 (2.86 g, 20.66 mmol) in H2O (16 mL) followed by Pd(PPh3)4 (252 mg, 0.689 mmol) and heat at 60° C. for 1 h. Cool to RT, add EtOAc, wash successively with H2O, satd. NaHCO3, then brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (1.277 g, 61%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 9.21 (d, J=0.8 Hz, 1H), 8.28 (s, 1H), 8.00 (s, 1H), 7.00 (d, J=12.4 Hz, 1H), 6.59 (d, J=9.3 Hz, 1H), 5.08 (s, 2H), 2.42 (s, 3H), 1.85 (s, 3H); MS (ESI) m/z: 302.1 (M+H+).

Workup

customSparge
temperatureCool to RT
washwash successively with H2O
dry with materialNaHCO3, then brine, dry over Na2SO4
concentrationconcentrate to dryness
custompurify via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record: ord-99b1d9dade2546e2b3c39c9013e88c9f
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187474B2

Reaction notes

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