Sodium Carbonate → N-(6-chloro-4'-{[(cyclopropylmethyl)amino]carbonyl}-1,1'-biphenyl-3-yl)-3-furamide

HRID 2114152Notes

Reaction equation

HRID 2114152 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[CH:16]=[CH:15][O:14][CH:13]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:17]1([CH2:20][NH:21][C:22](=[O:38])[C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:8][C:7]1[C:2]([C:26]2[CH:27]=[CH:28][C:23]([C:22]([NH:21][CH2:20][CH:17]3[CH2:19][CH2:18]3)=[O:38])=[CH:24][CH:25]=2)=[CH:3][C:4]([NH:9][C:10]([C:12]2[CH:16]=[CH:15][O:14][CH:13]=2)=[O:11])=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 11483451N-Cyclopropylmethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamideHCID 69204621N-(3-Bromo-4-chlorophenyl)-3-furancarboxamide2×

Product 1

HCID 44578612N-(6-chloro-4'-{[(cyclopropylmethyl)amino]carbonyl}-1,1'-biphenyl-3-yl)-3-furamide

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

N-(3-Bromo-4-chlorophenyl)-3-furamide (Intermediate 1, 63 mg), N-cyclopropylmethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzamide (60 mg), tetrakis(triphenylphosphine) palladium (5 mg) and aqueous sodium carbonate (2N, 0.5 ml) were mixed in DMF (1.2 ml) and heated at 80° C. under nitrogen for 18 hrs. The cooled reaction was absorbed onto silica, applied to an SPE (Si) and eluted with an ethyl acetate/cyclohexane gradient (0-100% ethyl acetate). The product fractions were reduced to dryness under vacuum and triturated with ether to give N-(6-chloro-4′-{[(cyclopropylmethyl)amino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide. NMR; δH [2H6]—DMSO 10.10,(1H, s), 8.65,(1H, t), 8.38,(1H, s), 7.94,(2H, d), 7.80,(3H, m), 7.54,(3H, m), 6.98,(1H, s), 3.16,(2H, t), 1.06,(1H, m), 0.43,(2H, m), 0.24,(2H, m). LCMS MH+395/397, retention time 3.32 minutes.

Workup

  1. customThe cooled reaction
  2. customwas absorbed onto silica
  3. washeluted with an ethyl acetate/cyclohexane gradient (0-100% ethyl acetate)
  4. customtriturated with ether

Sources & evidence

ORD record
ord-1327a1cca5dd405a937de0365cda604c
Source dataset
uspto-grants-2008_10
Patent number
US07432289B2

Reaction notes

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