Potassium Phosphate, Tribasic → [2-(5-Chloro-2-fluoro-phenyl)-quinolin-4-yl]-(3-nitro-pyridin-4-yl)-amine

HRID 877279Notes

Reaction equation

HRID 877279 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH:3]=1.[N+:20]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[NH2:29])([O-:22])=[O:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)(CC)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:16]1[CH:15]=[CH:14][C:13]([F:19])=[C:12]([C:4]2[CH:3]=[C:2]([NH:29][C:28]3[CH:27]=[CH:26][N:25]=[CH:24][C:23]=3[N+:20]([O-:22])=[O:21])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 5488034-Amino-3-nitropyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 671727124-Bromo-2-(5-chloro-2-fluoro-phenyl)-quinoline

Product 1

HCID 67173069[2-(5-Chloro-2-fluoro-phenyl)-quinolin-4-yl]-(3-nitro-pyridin-4-yl)-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 64052-Methyl-2-butanolSolvent

Procedure

10 g 4-Bromo-2-(5-chloro-2-fluoro-phenyl)-quinoline (cf. Example 5; M 336.59), and 4.13 g of 3-nitro-4-amino pyridine in 500 ml tert. amylalcohol were treated under argon with 272 mg Pd2(dba)3 (ABCR) and 0.69 g Xanthphos (ABCR) under basic conditions adjusted with 12.6 g K3PO4 at 117° C. external (100° C. internal temperature) for 6.5 hrs. Work-up with ethyl acetate extract washed with aqueous 5% KHSO4 solution (pH 2) and aqueous 5 NaHCO3 solution yielded after drying with Na2SO4, filtration and washings with methanol 6.6 g yellow powder of correct mass M+H+ 395 and Rt˜2.67 min and Rf˜0.44 in TLC on silica in petrolether/EE 2:1.

Workup

  1. customexternal (100° C. internal temperature)
  2. customfor 6.5 hrs
  3. extractionWork-up with ethyl acetate extract
  4. washwashed with aqueous 5% KHSO4 solution (pH 2) and aqueous 5 NaHCO3 solution
  5. customyielded
  6. dry with materialafter drying with Na2SO4, filtration and washings with methanol 6.6 g yellow powder of correct mass M+H+ 395 and Rt˜2.67 min and Rf˜0.44 in TLC on silica in petrolether/EE 2:1

Sources & evidence

ORD record
ord-2841742e6ba749dc98ce64f057ea28a5
Source dataset
uspto-grants-2015_03
Patent number
US08987301B2

Reaction notes

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