Hydrochloric Acid → HCID 56940947, compound

HRID 1254460Notes

Reaction equation

HRID 1254460 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]([O:34]CC)=[O:33])=[CH:26][CH:25]=3)=[C:13](/[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22]C)\[CH2:14][CH3:15])=[CH:9][CH:10]=2)[CH:5]=[N:4]1.B(Br)(Br)Br.[Li+].[OH-].Cl>C(Cl)Cl.C1COCC1.CCO.O>[OH:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1/[C:13](/[CH2:14][CH3:15])=[C:12](\[C:24]1[CH:25]=[CH:26][C:27](/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33])=[CH:28][CH:29]=1)/[C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[NH:3][N:4]=[CH:5]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 3939Lithium HydroxideHCID 25134Boron tribromideHCID 56940945HCID 56940945, compound

Product 1

HCID 56940947HCID 56940947, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21873804Tetrahydrofuran ethanolSolvent

Conditions

Temperature
-78 °C

Procedure

A 10-mL recovery flask equipped with a magnetic stir bar, a rubber septum and N2 inlet was charged with (E)-ethyl 3-(4-((E)-1-(1H-indazol-5-yl)-2-(2-methoxyphenyl)but-1-en-1-yl)phenyl)acrylate (145 mg, 0.32 mmol, an intermediate in the synthesis of Compound 12) in DCM (6 mL). This solution was cooled down to −78° C. in an IPA/dry ice-bath. Then, BBr3 (241 mg, 0.96 mmol) was added dropwise via a syringe. The reaction mixture was gradually warmed to 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. Then, this crude product was dissolved in THF-EtOH (1:1, 6 mL), and aqueous LiOH (0.15 g, 6.4 mmol) was added at room temperature. The resulting mixture was stirred at this temperature overnight. Reaction was monitored by LCMS. Upon completion, 1N aqueous HCl was added until pH was 3. Then, the mixture was diluted with water and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with water (100 mL), washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a reversed phase C-18 column eluted with 40-100% acetonitrile in water in the presence of 0.1% TFA affording the title compound. 1H NMR (300 MHz, DMSO-d6): δ 13.07 (s, 1H), 12.34 (br, 1H), 9.33 (br, 1H), 8.08 (d, 1H), 7.65 (s, 1H), 7.53 (d, 1H), 7.40 (d, 1H), 7.32 (d, 2H), 7.15 (dd, 1H), 7.00-6.94 (m, 3H), 6.81-6.76 (m, 2H), 6.57 (dt, 1H), 6.34 (d, 1H), 2.43-2.30 (m, 2H), 0.88 (t, 3H); LCMS: 411 (M+H)+.

Workup

  1. customA 10-mL recovery flask equipped with a magnetic stir bar
  2. temperatureThe reaction mixture was gradually warmed to 0° C. for 1 h
  3. customUpon completion, the reaction was quenched with methanol (5 mL) at 0° C
  4. concentrationThe resulting mixture was concentrated under reduced pressure
  5. customto give the crude product
  6. customReaction
  7. extractionextracted with ethyl acetate (3×100 mL)
  8. washThe combined organic layers were washed with water (100 mL)
  9. washwashed with brine (50 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-d48215e8a66647d08f681d6d65a6270c
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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