p-Toluenesulfonic acid → HCID 136408152, compound

HRID 922386Notes

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]([CH:8]=O)[CH:5]=[CH:4][CH:3]=1.[NH2:10][C:11]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:12]=1[C:13]([NH2:15])=[O:14].C1(C)C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+]>CC(N(C)C)=O>[Br:1][C:2]1[N:7]=[C:6]([C:8]2[NH:15][C:13](=[O:14])[C:12]3[C:11](=[CH:19][C:18]([F:20])=[CH:17][C:16]=3[F:21])[N:10]=2)[CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 6-bromopicolinaldehyde (2.8 g, 15 mmol), 2-amino-4,6-difluorobenzamide (2.5 g, 10 mmol), p-toluenesulfonic acid (4.2 g, 22 mmol), NaHSO3 (2.6 g, 25 mmol) and DMA (40 mL) was heated at 110° C. for 48 h in a sealed tube. The reaction mixture was cooled to room temperature and partitioned between water and EtOAc (25 mL). The aqueous phase was extracted with EtOAc (2×25 mL). The organic layers were combined, dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The product was purified by crystallization (EtOAc) to provide the title compound (500 mg, 15%): 1H NMR (500 MHz, DMSO-d6) δ 11.97 (s, 1H), 8.32 (d, J=7.7, 0.7 Hz, 1H), 8.05-7.96 (m, 1H), 7.91 (dd, J=7.7, 0.7 Hz, 1H), 7.46-7.29 (m, 2H).

Workup

temperatureThe reaction mixture was cooled to room temperature
custompartitioned between water and EtOAc (25 mL)
extractionThe aqueous phase was extracted with EtOAc (2×25 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
customthe solvent was removed under reduced pressure
customThe product was purified by crystallization (EtOAc)

Sources & evidence

ORD record: ord-a9fda970d73344e4813c1cef4b638315
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278940B2

Reaction notes

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