Biphenyl → Urea

HRID 2086006Notes

Reaction equation

HRID 2086006 reaction equation
S(OC1C=CC(C[C@@H](C(O)=O)[NH2:15])=CC=1)(C(F)(F)F)(=O)=O.[C:21]1([S:36](Cl)(=[O:38])=[O:37])[C:34]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27](=[O:35])[NH:26][C:25]=2[CH:24]=[CH:23][CH:22]=1.C1(C2C=CC=CC=2)C=CC=CC=1>[Pd].C(N(CC)CC)C>[C:21]1([S:36]([NH2:15])(=[O:38])=[O:37])[C:34]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27](=[O:35])[NH:26][C:25]=2[CH:24]=[CH:23][CH:22]=1.[C:27]([NH2:15])([NH2:26])=[O:35]

Participants

7

Reactant 3

HCID 7095BiphenylHCID 22727942HCID 22727942, compoundHCID 87519022HCID 87519022, compound

Product 2

HCID 1176UreaHCID 69865847HCID 69865847, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8471TriethylamineSolvent

Procedure

Scheme 3 below illustrates schematically the preparation of compounds Example 13 through Example 19. The 3-substituted (5H)phenanthridin-6-one skeleton of this invention can be constructed in a conventional manner using Schmidt method with fluoren-9-one 5 as starting material and sodium azide as an insertion agent in acidic condition (Chida, N.: Ohtsuka. M.: Ogawa, S. Tetrahedron Lett. 1991, 32, 4525). The fluoren-9-one ring may be generically substituted as set forth in the drawing. Such fluoren-9-one starting derivatives are known in the chemistry literature and accessible by processes known to one skilled in the art. This Schmidt method normally generates a pair of regioisomer mixtures 6 and 7, which may be separated and purified by chromatography or crystallization. For example, a mixture of 2(fluoren-9-one)carboxylic acid (0.25 g) and sodium azide (0.25 g) in c-sulfuric acid (10 mL) was stirred at 0° C. for 30 minutes at 25° C. for 10 hours, and then poured into ice-cold water (100 mL). A yellow precipitation appeared upon adjusting the solution to pH 7 with sodium hydroxide. The precipitation, a regioisomer mixture of 3-[6(5H)phenanthridinone]carboxylic acid 6 and of 8-[6(5H)phenanthridinone]carboxylic acid 7, was collected by filtration and purified on silica gel column to give a pure isomer of 3-[6(5H)phenanthridinone]carboxylic acid 6 (0.1 g), mp 300° C. (dec.). 1H-NMR (400 MHz, DMSO-d6), 13.19 (bs, 1H), 11.88 (s, 1H), 8.58 (d, 1H, J=8 Hz), 8.52 (d, 1H, J=8 Hz), 8.35 (d, 1H, J=8 Hz), 8.01 (s, 1H), 7.89 (t, 1H, J=8 Hz), 7.76 (t, 1H, J=8 Hz), 7.72 (d, 1H, J=8 Hz). There are several ways, such as Ullman reactions (Synthesis, 1997, p.1273-1275 “Synthesis and Characterization of Some Nitrobenzanthrones: Suspected New Mutagens in Atmospheric Environment”, Hitomi Suzuki, Takeji Enya, Yoshiharu Hizamatsu) and Suzuki couplings (J. Organic. Chememistry., 1992, 57, p.379-381. “A simple asymetric sythesis of 4-arylphenylalanines vis palladium-catalyzed cross coupling reaction of arylboric acids with tyrosine triflate” W.-C. Shieh; J. A. Carlson), to construct substituted 6(5H)Phenanthridinone carboxylic acid and 6(5H)Phenanthridinone sulfonyl chloride. Formation of substituted 6(5H)Phenanthridinone using biphenyl compounds can be carried out by a variety of conditions known to those skilled in the art. 3-[6(5H)Phenanthridinone]carboxylic acid 6 can be routinely converted to 3-[6(5H)Phenanthridinone]carbonyl chloride 7 using thionyl chloride neat at 60° C. Amidation of desired regioisomer of 3-[6(5H)phenanthridinone]sulfonyl chloride 6 or 3-[6(5H)Phenanthridinone]carbonyl chloride 7 with R′ substituted primary amine using triethyl amine (TEA) as base provides (5H)phenanthridin-6-one sulfonamide and carbamide of Example 13-19.

Workup

  1. customsuch as Ullman reactions (Synthesis, 1997

Sources & evidence

ORD record
ord-7a314de67aa74b1d84acd61474dc5c03
Source dataset
uspto-grants-2004_04
Patent number
US06723733B2

Reaction notes

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