Hydrochloric Acid → HCID 118005843, compound

HRID 715142Notes

Reaction equation

HRID 715142 reaction equation
[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16]3[C:17]([CH3:28])=[N:18][C:19]4[C:24]([CH:25]=3)=[CH:23][N:22]=[C:21]([NH:26][CH3:27])[CH:20]=4)[C:13]([CH3:29])=[CH:12][C:11]=2[F:30])=[O:8])[CH2:3][CH2:2]1.[ClH:31]>C(#N)C>[ClH:31].[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16]3[C:17]([CH3:28])=[N:18][C:19]4[C:24]([CH:25]=3)=[CH:23][N:22]=[C:21]([NH:26][CH3:27])[CH:20]=4)[C:13]([CH3:29])=[CH:12][C:11]=2[F:30])=[O:8])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 71737482HCID 71737482, compound

Product 1

HCID 118005843HCID 118005843, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Add Pd2(dba)3 (0.020 g, 0.022 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl [t-butyl X-Phos] (0.019 g, 0.045 mmol), methylamine (2.0M in THF, 1.114 mL, 2.228 mmol) and Cs2CO3 (0.436 g, 1.337 mmol) to a solution of 1-(5-(7-chloro-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(2-cyclopropylethyl)urea (0.184 g, 0.446 mmol) in dioxane (4 mL) and heat at 90° C. for 3 h. Cool to RT, remove the solids via filtration, rinse with DCM, then THF, concentrate the filtrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford 1-(2-cyclopropylethyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea (108 mg, 59%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.82 (s, 1H), 8.28 (d, J=2.4 Hz, 1H), 7.95 (d, J=8.5 Hz, 1H), 7.85 (s, 1H), 7.16 (d, J=12.4 Hz, 1H), 6.78-6.72 (m, 1H), 6.59 (m, 1H), 6.52 (s, 1H), 3.10 (q, J=6.5 Hz, 2H), 2.82 (d, J=5.0 Hz, 3H), 2.26 (s, 3H), 1.95 (s, 3H), 1.37 (m, 2H), 0.70 (m, 1H), 0.35 (m, 2H), 0.04 (m, 2H); MS(ESI) m/z: 408.2 (M+H+). Suspend 1-(2-cyclopropylethyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, (0.108 g, 0.265 mmol) in acetonitrile (4 mL), treat with 0.5 M HCl (0.53 mL, 0.265 mmol), freeze and lyophilize the resulting clear solution to provide the title compound. MS(ESI) m/z: 408.2 (M+H+).

Sources & evidence

ORD record
ord-7a3853a98eef483abdf537f007afdc6e
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

Loading…