Acetic Acid → 4-bromo-N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)picolinamide

HRID 1423330Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:15]=[C:14]([C:16]([NH:18][NH2:19])=O)[S:13][CH:12]=2)=[O:9])[CH:3]=1.[CH3:20][N:21]([CH3:24])C=O.CN(C)[C:27](=O)[CH3:28].C1(N)CC1.C(O)(=O)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:15]=[C:14]([C:16]3[N:21]([CH:24]4[CH2:28][CH2:27]4)[CH:20]=[N:19][N:18]=3)[S:13][CH:12]=2)=[O:9])[CH:3]=1

Participants

Conditions

Temperature: 145 °C

Procedure

The 4-bromo-N-(5-(hydrazinecarbonyl)thiophen-3-yl)picolinamide (600 mg, 1.8 mmol) and toluene (9 mL) were added to a sealable vial, N,N-dimethylformamide•N,N-dimethylacetamide (600 μL, 4.5 mmol) was added and the reaction was stirred for 5 minutes. Cyclopropyl amine (490 μL, 7.2 mmol), and acetic acid (100 μL, 1.8 mmol) were added and the reaction was heated in a microwave reactor at 145° C. for 30 minutes. The solvent was removed under reduced pressure, and the product, 4-bromo-N-(5-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiophen-3-yl)picolinamide 350 mg (50%), was isolated by precipitation from acetonitrile/methanol. Alternatively, the reaction mixture may be purified by flash chromatography. M+1=390.1

Workup

additionwas added
customThe solvent was removed under reduced pressure

Sources & evidence

ORD record: ord-b33190f59d034d5697ee2e51deb8e42a
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927582B2

Reaction notes

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