p-Toluenesulfonic acid → HCID 24783657, compound

HRID 1485345Notes

Reaction equation

Cl[C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13]3[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([CH:23]([CH3:25])[CH3:24])[N:3]=1.[Br:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:26][C:27]1[CH:33]=[CH:32][C:30]([NH:31][C:2]2[C:12]3[CH2:11][CH2:10][N:9]([C:13]4[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][N:14]=4)[CH2:8][CH2:7][C:6]=3[N:5]=[C:4]([CH:23]([CH3:24])[CH3:25])[N:3]=2)=[CH:29][CH:28]=1

Participants

Conditions

Temperature: 130 °C

Procedure

Step E A mixture of 4-chloro-2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine (50 mg, 0.14 mmol), 4-bromoaniline (35 mg, 0.36 mmol), and p-toluenesulfonic acid (51 mg, 0.27 mmol) in toluene (2 mL) was heated in a sealed tube at 130° C. for 18 h. The mixture was cooled, diluted with satd. aq. NaHCO3, and extracted with EtOAc. The organic layer was dried (Na2SO4) and concentrated. The residue was purified (FCC) to give the title compound (57 mg, 77%). MS (ESI): mass calcd. for C23H23BrF3N5, 505.11; m/z found, 506.1 [M+H]+. 1H NMR (CDCl3): 8.41-8.39 (m, 1H), 7.90-7.87 (m, 1H), 7.61-7.56 (m, 2H), 7.48-7.43 (m, 2H), 6.99-6.95 (m, 1H), 6.49 (s, 1H), 3.68-3.65 (m, 2H), 3.63-3.60 (m, 2H), 3.25-3.21 (m, 2H), 3.08-2.99 (m, 1H), 2.98-2.94 (m, 2H), 1.32 (d, J=6.9 Hz, 6H).

Workup

temperatureThe mixture was cooled
additiondiluted with satd
extractionaq. NaHCO3, and extracted with EtOAc
dry with materialThe organic layer was dried (Na2SO4)
concentrationconcentrated
customThe residue was purified (FCC)

Sources & evidence

ORD record: ord-ea0d03730078498d881d589b768b5fc2
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422293B2

Reaction notes

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