Nitrogen → HCID 56943021, compound

HRID 1254459Notes

Reaction equation

HRID 1254459 reaction equation
N#N.[NH:3]1[C:11]2[C:6](=[CH:7][C:8](/[C:12](/[C:24]3[CH:29]=[CH:28][C:27](/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33])=[CH:26][CH:25]=3)=[C:13](/[C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22]C)[CH:17]=3)\[CH2:14][CH3:15])=[CH:9][CH:10]=2)[CH:5]=[N:4]1.B(Br)(Br)Br>C(Cl)Cl>[OH:22][C:18]1[CH:17]=[C:16](/[C:13](/[CH2:14][CH3:15])=[C:12](\[C:24]2[CH:29]=[CH:28][C:27](/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33])=[CH:26][CH:25]=2)/[C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[NH:3][N:4]=[CH:5]3)[CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 947NitrogenHCID 25134Boron tribromideHCID 56943019HCID 56943019, compound2×

Product 1

HCID 56943021HCID 56943021, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 10-mL recovery flask equipped with a magnetic stir bar, a rubber septum and N2 inlet was charged with (E)-3-(4-((E)-1-(1H-indazol-5-yl)-2-(3-methoxyphenyl)but-1-en-1-yl)phenyl)acrylic acid (30 mg, 0.07 mmol, Compound 5) and DCM (1.4 mL). This solution was cooled down to 0° C. in an ice-bath. Then, BBr3 (88 mg, 0.35 mmol) was added dropwise via a syringe. The reaction mixture was stirred at 0° C. for 1 h. Upon completion, the reaction was quenched with methanol (5 mL) at 0° C. The resulting mixture was concentrated under reduced pressure to give the crude product that was directly purified on a reversed phased C-18 column eluted with 40-100% acetonitrile in water in the presence of 0.1% TFA affording the title compound as an off-white solid (11 mg). 1H NMR (300 MHz, DMSO-d6): δ 13.11 (s, 1H), 12.32 (br, 1H), 9.23 (s, 1H), 8.08 (s, 1H), 7.62 (s, 1H), 7.52 (d, 1H), 7.45-7.35 (m, 3H), 7.12 (d, 1H), 7.00 (t, 1H), 6.90 (d, 2H), 6.59-6.53 (m, 3H), 6.36 (d, 1H), 2.37 (q, 2H), 0.89 (t, 3H); LCMS: 411 (M+H)+.

Workup

  1. customA 10-mL recovery flask equipped with a magnetic stir bar
  2. customUpon completion, the reaction was quenched with methanol (5 mL) at 0° C
  3. concentrationThe resulting mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-60df524e9f3941909174a3ee3be936bb
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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