5-Bromo-4-fluoro-2-iodotoluene → N-(7-(4-bromo-5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468965

Reaction equation

HRID 468965 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)O1.[Br:26][C:27]1[CH:32]=[C:31]([CH3:33])[C:30](I)=[CH:29][C:28]=1[F:35]>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].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>[Br:26][C:27]1[C:28]([F:35])=[CH:29][C:30]([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]4[CH2:23][CH2:24]4)=[O:21])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)=[C:31]([CH3:33])[CH:32]=1

Participants

7

Reactant 2

HCID 121872165-Bromo-4-fluoro-2-iodotolueneHCID 67976378N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67974845N-(7-(4-bromo-5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamideYield 65%

Reagents, catalysts & solvents 4

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-isoquinolyl]cyclopropanecarboxamide (500 mg, 1.48 mmol), 1-bromo-2-fluoro-4-iodo-5-methyl-benzene (559 mg, 1.77 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (105 mg, 0.15 mmol) in ACN (6 mL) and saturated aqueous sodium carbonate (1 mL) was heated under microwave irradiation (Biotage) 120° C. for 20 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 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 (12 g, Silica, 0-60% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a white solid (385, 65%), which was used in the next step without further purification.

Workup

  1. washwashed with water (50 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 (12 g, Silica, 0-60% ethyl acetate in heptane)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-bcd2577d65524a3ea2ddc064afe20b68
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Linked notes

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