Sodium Bicarbonate → Tert-butyl 2-({5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-1,1'-biphenyl-4-yl}carbonyl)hydrazinecarboxylate

HRID 31420Notes

Reaction equation

HRID 31420 reaction equation
[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:7]=2)[CH2:3][CH2:2]1.CC(C)(C)C([NH:28][NH:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][C:34](Br)=[CH:33][CH:32]=1)=O.[C:41](=[O:44])([O-])[OH:42].[Na+]>CC(O)C.C(OCC)(=O)C.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>[CH:1]1([NH:4][C:5]([C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:34]3[CH:33]=[CH:32][C:31]([C:30]([NH:29][NH:28][C:41]([O:42][C:6]([CH3:11])([CH3:7])[CH3:5])=[O:44])=[O:38])=[CH:36][CH:35]=3)[CH:7]=2)=[O:23])[CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 47826934-bromo-N'-(2,2-dimethylpropanoyl)benzohydrazide2×HCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2×

Product 1

HCID 69316615Tert-butyl 2-({5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-1,1'-biphenyl-4-yl}carbonyl)hydrazinecarboxylate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

N-Cyclopropyl-5-fluoro-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 32) (3.27 g), 4-bromo-benzoic acid N′-(2,2-dimethyl-propionyl)-hydrazide (Intermediate 31) (3.39 g), tetrakis(triphenylphosphine)palladium (238 mg) and aqueous sodium hydrogen carbonate (1M, 21.6 ml) were mixed in propan-2-ol (20 ml) and heated at 90° C. under nitrogen for 18 hours. The cooled reaction mixture was reduced to dryness under vacuum, the residue partially dissolved in ethyl acetate and filtered. The filtrate was absorbed onto silica and purified by chromatography on silica biotage columns (2×100 g), eluting with ethyl acetate/cyclohexane (2:3). The product fractions were reduced to dryness under vacuum to give tert-butyl 2-({5′-[(cyclopropylamino)carbonyl]-3′-fluoro-2′-methyl-1,1′-biphenyl-4-yl}carbonyl)hydrazinecarboxylate.

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered
  3. customThe filtrate was absorbed onto silica
  4. custompurified by chromatography on silica biotage columns (2×100 g)
  5. washeluting with ethyl acetate/cyclohexane (2:3)

Sources & evidence

ORD record
ord-815eec6cb8dd45079998f14e3ae2fc01
Source dataset
uspto-grants-2008_09
Patent number
US07425555B2

Reaction notes

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