Sodium Carbonate → methyl 5-(7-((1S,2S)-2-fluorocyclopropanecarboxamido)-2,6-naphthyridin-3-yl)-4-methylpicolinate

HRID 468941Notes

Reaction equation

HRID 468941 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([C@@H:15]3[CH2:17][C@@H:16]3[F:18])=[O:14])[N:8]=[CH:9]2)=[CH:4][N:3]=1.[CH3:19][C:20]1[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][N:23]=[C:22]([C:35]([O:37][CH3:38])=[O:36])[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:18][C@H:16]1[CH2:17][C@H:15]1[C:13]([NH:12][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([C:25]3[C:20]([CH3:19])=[CH:21][C:22]([C:35]([O:37][CH3:38])=[O:36])=[N:23][CH:24]=3)[N:3]=[CH:4]2)=[CH:9][N:8]=1)=[O:14]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 67977255Methyl 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylateHCID 86674973(1S,2S)-N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamide

Product 1

HCID 71115323methyl 5-(7-((1S,2S)-2-fluorocyclopropanecarboxamido)-2,6-naphthyridin-3-yl)-4-methylpicolinateYield 52.4%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of (1S,2S)—N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamide (100 mg, 0.376 mmol), methyl 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (156 mg, 0.565 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (26.6 mg, 0.038 mmol) and saturated aqueous sodium carbonate solution (0.1 mL) in acetonitrile (1 mL) was heated under microwave irradiation (Biotage) at 130° C. for 30 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a pale yellow solid (75 mg, 52%), which was used in the next step without further purification.

Workup

  1. washwashed with water (20 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-389fa59d88cb47d2b32068322ffc971a
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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