Diisopropylethylamine → 5-amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid amide

HRID 2041046Notes

Reaction equation

[C:1]([C:3](=[C:7](SC)[S:8][CH3:9])[C:4]([NH2:6])=[O:5])#[N:2].FC(F)(F)C(O)=O.[CH:19]1([NH:22][C:23](=[O:33])[C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([NH:31][NH2:32])[CH:25]=2)[CH2:21][CH2:20]1.C(N(C(C)C)CC)(C)C>C(O)C>[NH2:2][C:1]1[N:31]([C:26]2[CH:25]=[C:24]([C:23](=[O:33])[NH:22][CH:19]3[CH2:21][CH2:20]3)[CH:29]=[CH:28][C:27]=2[CH3:30])[N:32]=[C:7]([S:8][CH3:9])[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 2-cyano-3,3-bis-methylsulfanyl-acrylamide 12 (100 mg, 0.574 mmol) in ethanol (5 ml) was added N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetic acid salt (0.183 g, 0.574 mmol) and diisopropylethylamine (0.100 ml, 0.574 mmol). The mixture was heated to 65° C. for 18 h. The mixture was cooled to room temperature. Solvents were removed in vacuo. EtOAc was added to the residue and a solid precipitated. The solid was collected on a fitted funnel and was washed with EtOAc and ether to give the desired 5-amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid amide 13. HPLC (4 minute 10-90 gradient) tR 1.98 min; MS m/z 439.08 [M+H]+; 1H NMR (DMSO-d6, 500 MHz) δ 8.47 (d, J=3.7, 1H), 7.90 (d, J=7.9, 1 H), 7.78 (s, 1H), 7.49 (d, J=8.0, 1H), 6.81 (bs, 2H), 6.30 (s, 2H), 2.86 (m, 1H), 2.45 (s, 3H), 2.11 (s, 3H), 0.68 (m, 2H), 0.57 (m, 2H) ppm.

Workup

temperatureThe mixture was cooled to room temperature
customSolvents were removed in vacuo
additionEtOAc was added to the residue
customa solid precipitated
customThe solid was collected on a fitted funnel
washwas washed with EtOAc and ether

Sources & evidence

ORD record: ord-d9ffb25ab16c4eb7aff62efad2988a16
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580838B2

Reaction notes

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