Ethyl Acetate → 6-chloro-N3-cyclopropyl-N4'-(cyclopropylmethyl)-1,1'-biphenyl-3,4'-dicarboxamide

HRID 1272721Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[Cl:14])[C:5]([NH:7][CH:8]1[CH2:10][CH2:9]1)=[O:6].[CH:15]1([CH2:18][NH:19][C:20](=[O:36])[C:21]2[CH:26]=[CH:25][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>CN(C=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>[Cl:14][C:13]1[C:2]([C:24]2[CH:25]=[CH:26][C:21]([C:20]([NH:19][CH2:18][CH:15]3[CH2:17][CH2:16]3)=[O:36])=[CH:22][CH:23]=2)=[CH:3][C:4]([C:5]([NH:7][CH:8]2[CH2:10][CH2:9]2)=[O:6])=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 85 °C

Procedure

3-Bromo-4-chloro-N-cyclopropylbenzamide (Intermediate 18, 55 mg), N-cyclopropylmethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzamide (Intermediate 19, 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 85° C. under nitrogen for 18 hrs. Ethyl acetate was added to the cooled reaction, the reaction filtered and the filtrate reduced to dryness under vacuum. The residue was applied to a SPE cartridge (Si, 5 g) and eluted with an ethyl acetate/cylohexane gradient (0–100% ethyl acetate). The product fractions were reduced to dryness under vacuum to give 6-chloro-N3-cyclopropyl-N4′-(cyclopropylmethyl)-1,1′-biphenyl-3,4′-dicarboxamide.

Workup

filtrationthe reaction filtered
washeluted with an ethyl acetate/cylohexane gradient (0–100% ethyl acetate)

Sources & evidence

ORD record: ord-bf941fd052e3400d822107f19a213d2b
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07208629B2

Reaction notes

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