2-Aminobiphenyl → HCID 117599646, compound

HRID 593311Notes

Reaction equation

HRID 593311 reaction equation
F[C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[C:4]#[N:5].[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CC(C)([O-])C.[K+]>CS(C)=O.O>[C:15]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[NH:13][C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 70152-AminobiphenylHCID 5194172-Fluoro-5-nitrobenzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 117599646HCID 117599646, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2-fluoro-5-nitrobenzonitrile (690 mg, 4.13 mmol, 1 equiv) and 2-aminobiphenyl (700 mg, 4.13 mmol, 1 equiv) in anhydrous DMSO (20 mL) at room temperature was added potassium tert-butoxide (930 mg, 8.26 mmol, 2 equiv). After 16 h, the reaction mixture was diluted with water, and extracted into EtOAc (×3). The EtOAc extractions were combined, washed with water (×5), brine, dried (Na2SO4), filtered and concentrated. The crude residue was dry-loaded onto silica gel and purified by flash column chromatography (CH2Cl2/Hex/EtOAc, 10:10:1) to afford 2-([1,1′-biphenyl]-2-ylamino)-5-nitrobenzonitrile as an orange solid (728 mg, 56%): δH (CDCl3, 400 MHz) 8.31 (d, J=2.4, 1H, Ar), 8.10 (dd, J=9.6, 2.4, 1H, Ar), 7.50-7.24 (m, 9H, Ar), 6.92 (d, J=9.6, 1H, Ar), 6.79 (s, 1H, NH); δC (CDCl3, 100 MHz) 152.2, 138.5, 137.9, 137.5, 134.4, 131.6, 129.7, 129.5, 128.9, 128.8, 128.6, 128.2, 127.6, 125.4, 115.2, 112.5, 96.7), which was subsequently hydrolyzed (1.17 mmol scale) with NaOH (140 mg, 3.52 mmol, 2 equiv) in a 1:1:1 mixture of dioxane/EtOH/H2O (12 mL) at reflux for 48 h. The reaction mixture was concentrated to dryness, and then partitioned between Et2O and H2O to remove neutral organics. The aqueous layer was acidified with 1M HCl, and then extracted with EtOAc (×3). The EtOAc extractions were combined, washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was dry-loaded onto silica gel and purified by flash column chromatography (CH2Cl2/MeOH/AcOH, 92:7:1) to deliver the title compound 2-([1,1′-biphenyl]-2-ylamino)-5-nitrobenzoic acid (SF-3-103B) as an orange solid (293 mg, 75%): δH (CDCl3+MeOH-d4, 400 MHz) 10.01 (s, 1H, OH), 8.80 (d, J=2.4, 1H, NH), 7.98 (dd, J=9.6, 2.4, 1H, Ar), 7.43-7.17 (m, 11H, Ar), 6.82 (d, J=9.6, 1H, Ar); δC (CDCl3, 100 MHz) 169.2, 153.2, 138.3, 138.2, 137.0, 135.4, 131.4, 129.5, 129.1, 128.8, 128.5, 128.4, 127.5, 126.9, 126.0, 113.0, 110.2.

Workup

  1. extractionextracted into EtOAc (×3)
  2. extractionThe EtOAc extractions
  3. washwashed with water (×5), brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash column chromatography (CH2Cl2/Hex/EtOAc, 10:10:1)

Sources & evidence

ORD record
ord-8c77fdcd80e943529403a531536f8245
Source dataset
uspto-grants-2016_01
Patent number
US09242944B2

Reaction notes

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