Boron tribromide → US10023592, Example 80

HRID 518303Notes

Reaction equation

HRID 518303 reaction equation
B(Br)(Br)Br.[CH2:5]([S:7]([C:10]1[CH:11]=[CH:12][C:13]([O:34]C)=[C:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)[CH:24]=3)[C:19](=[O:32])[N:18]([CH3:33])[CH:17]=2)[CH:15]=1)(=[O:9])=[O:8])[CH3:6]>C(Cl)Cl>[CH2:5]([S:7]([C:10]1[CH:11]=[CH:12][C:13]([OH:34])=[C:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)[CH:24]=3)[C:19](=[O:32])[N:18]([CH3:33])[CH:17]=2)[CH:15]=1)(=[O:8])=[O:9])[CH3:6]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 1180214764-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one

Product 1

HCID 118021404US10023592, Example 80Yield 36.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At −78° C., a 4 M solution of BBr3 (2.3 mL, 9.2 mmol) in CH2Cl2 was added to the title compound of Example 79 (200.0 mg, 0.458 mmol) in dry CH2Cl2 (8 mL). The mixture was refluxed for 18 h. Extractive work up with CH2Cl2 and purification by silica gel chromatography (DCM:MeOH=100:1 to 20:1) gave the title compound (70 mg, 36.1%) as a brown solid. 1H NMR (CDCl3, 400 MHz) δ 8.39 (d, J=8.4 Hz, 1H), 7.99 (s, 1H), 7.87 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.80 (s, 1H), 7.79 (s, 1H), 7.76 (d, J=1.6 Hz, 1H), 7.39 (s, 1H), 7.35 (d, J=1.2 Hz, 1H), 7.18 (d, J=8.8 Hz, 1H), 3.91 (s, 3H), 3.67 (s, 3H), 3.25 (q, J=7.6 Hz, 2H), 1.27 (t, J=7.6 Hz, 3H). LCMS: 424.0 (M+H)+

Workup

  1. temperatureThe mixture was refluxed for 18 h
  2. customExtractive work up with CH2Cl2 and purification by silica gel chromatography (DCM:MeOH=100:1 to 20:1)

Sources & evidence

ORD record
ord-996251fe827145d284a981196817ca9c
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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