Hydrochloric Acid → HCID 71607774, compound

HRID 2272365Notes

Reaction equation

HRID 2272365 reaction equation
Cl.[CH:2]1([C:5]2[C:6]([N:25]([C:30]3[CH:35]=[C:34]([CH2:36]OCOC)[C:33]([B:41]4[O:45]C(C)(C)C(C)(C)[O:42]4)=[C:32]([F:50])[CH:31]=3)[S:26]([CH3:29])(=[O:28])=[O:27])=[CH:7][C:8]3[O:12][C:11]([C:13]4[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=4)=[C:10]([C:20]([NH:22][CH3:23])=[O:21])[C:9]=3[CH:24]=2)[CH2:4][CH2:3]1>C1COCC1.CO.C(Cl)Cl>[CH:2]1([C:5]2[C:6]([N:25]([C:30]3[CH:31]=[C:32]([F:50])[C:33]4[B:41]([OH:42])[O:45][CH2:36][C:34]=4[CH:35]=3)[S:26]([CH3:29])(=[O:27])=[O:28])=[CH:7][C:8]3[O:12][C:11]([C:13]4[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=4)=[C:10]([C:20]([NH:22][CH3:23])=[O:21])[C:9]=3[CH:24]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 131732319HCID 131732319, compound

Product 1

HCID 71607774HCID 71607774, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Aqueous hydrochloric acid (4 mL, 1 N) was added to a solution of 5-cyclopropyl-6-(N-(3-fluoro-5-((methoxymethoxy)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methylsulfonamido)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (306 mg) in THF (4.0 mL) and MeOH (0.8 mL). The mixture was heated to 70° C. under N2 overnight. The mixture was cooled to room temperature and the organic solvent was removed under reduced pressure. The crude was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. MeOH (6 mL) was then added to the crude and stirred for 15 min. A white solid was formed which was filtered to give 170 mg crude product (90% purity). 50 mg crude product was purified by silica gel chromatography (0-100% EtOAc in DCM, then 0-10% MeOH in DCM) to give 5-cyclopropyl-6-(N-(7-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methylsulfonamido)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (17 mg, 6.24% yield). Another 120 mg crude product was washed with MeOH and dried to give 5-cyclopropyl-6-(N-(7-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methylsulfonamido)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (106 mg, 36.6% yield). 1H NMR (400 MHz, DMSO-d6) 8 ppm 0.50 (br. s., 1H), 0.81 (br. s., 2H), 0.97 (br. s., 1H), 2.06 (br. s., 1H), 2.84 (d, J=4.3 Hz, 3H), 3.48 (s, 3H), 4.95 (s, 2H), 7.02 (d, J=9.9 Hz, 1H), 7.20 (d, J=7.9 Hz, 2H), 7.41 (t, J=8.8 Hz, 2H), 7.97 (dd, J=8.5, 5.6 Hz, 2H), 8.04 (s, 1H), 8.49 (d, J=4.5 Hz, 1H), 9.28 (s, 1H). LCMS (m/z, ES+)=553 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthe organic solvent was removed under reduced pressure
  3. additionThe crude was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. additionMeOH (6 mL) was then added to the crude
  9. customA white solid was formed which
  10. filtrationwas filtered
  11. customto give 170 mg crude product (90% purity)
  12. custom50 mg crude product was purified by silica gel chromatography (0-100% EtOAc in DCM

Sources & evidence

ORD record
ord-32d8f0c8755c4891a9004618e4a82331
Source dataset
uspto-grants-2015_09
Patent number
US09119868B2

Reaction notes

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