Hydrogen Bromide → HCID 131732857, compound

HRID 576111Notes

Reaction equation

HRID 576111 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:10]=[C:11]([CH:16]2[C:25]3[C:20](=[CH:21][C:22]([C:27]4[N:28]=[N:29][C:30]([O:33]C)=[CH:31][CH:32]=4)=[C:23]([F:26])[CH:24]=3)[CH2:19][NH:18][CH2:17]2)[CH:12]=[CH:13][C:14]=1[Cl:15].Br>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:10]=[C:11]([CH:16]2[C:25]3[C:20](=[CH:21][C:22]([C:27]4[CH:32]=[CH:31][C:30](=[O:33])[NH:29][N:28]=4)=[C:23]([F:26])[CH:24]=3)[CH2:19][NH:18][CH2:17]2)[CH:12]=[CH:13][C:14]=1[Cl:15]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131732858HCID 131732858, compound

Product 1

HCID 131732857HCID 131732857, compoundYield 80%

Procedure

A mixture of 4-(3,4-dichlorophenyl)-6-fluoro-7-(6-methoxypyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline, trifluoroacetate salt (20 mg, 0.04 mmol, product of Step B in Example 21) and hydrobromic acid (aqueous, 48%) was heated to reflux for 1 hour. The mixture was cooled to room temperature and concentrated. The residue was purified by semi-preparative HPLC followed by lyophilization to give 4 6-(4-(3,4-dichlorophenyl)-6-fluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridazin-3(2H)-one, trifluoroacetate salt (16 mg, 80%) as a white solid: 1H NMR (CD3OD, 500 MHz) δ 7.84 (dd, J=9.9, 2.1 Hz, 1H), 7.74 (d, J=7.5 Hz, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.52 (d, J=2.0 Hz, 1H), 7.24 (dd, J=8.3, 2.0 Hz, 1H), 7.04 (d, J=9.9 Hz, 1H), 6.78 (d, J=11.7 Hz, 1H), 4.67-4.49 (m, 3H), 3.81 (dd, J=12.6, 6.0 Hz, 1H), 3.50 (dd, J=11.3, 11.3 Hz, 1H); ESI MS m/z 390 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1 hour
  3. concentrationconcentrated
  4. customThe residue was purified by semi-preparative HPLC

Sources & evidence

ORD record
ord-74c0c501969741dea64c2564e6b09786
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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