Hydrochloric Acid → HCID 68938521, compound

HRID 2095273Notes

Reaction equation

HRID 2095273 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:30])=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13]CC)=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18][O:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1.[C:31]1([CH3:40])[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[Cs+].O[Li].O.Cl>O.O1CCCC1>[F:30][C:5]1[CH:4]=[CH:3][C:2]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[CH3:40])=[C:10]2[C:6]=1[C:7]([CH2:16][CH2:17][CH2:18][O:19][C:20]1[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=[CH:22][CH:21]=1)=[C:8]([C:11]([OH:13])=[O:12])[NH:9]2

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 25953Cesium fluoride2×HCID 168937Lithium hydroxide, monohydrateHCID 27332672-Methylphenyl boronic acid2×HCID 2734635Tri-tert-butylphosphine tetrafluoroborate2×HCID 68936013HCID 68936013, compound

Product 1

HCID 68938521HCID 68938521, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of EXAMPLE 402D (47 mg), o-tolylboronic acid (19 mg), tris(dibenzylidineacetone)dipalladium(0) (4.6 mg), tri-t-butyl-phosphonium tetrafluoroborate (3.5 mg), cesium fluoride (45.6 mg) and tetrahydrofuran (1.5 ml) was stirred at ambient temperature under a nitrogen atmosphere overnight. Additional o-tolylboronic acid (9.5 mg), tris(dibenzylidineacetone)dipalladium(0) (2.3 mg), tri-t-butyl-phosphonium tetrafluoroborate (1.8 mg) and cesium fluoride (23 mg) were added and stirring was continued at ambient temperature overnight. LiOH—H2O (42 mg) and water (0.5 ml) were added and the mixture was heated overnight at 60° C. The reaction mixture was acidified with 1 M HCl (aq), extracted (3×5 ml) with ethyl acetate, dried (MgSO4), filtered and concentrated. The concentrate was slurried in methanol and filtered through a syringe filter. The filtrate was concentrated. The concentrate was purified by reverse phase HPLC (50-95% acetonitrile/water/0.1% trifluoroacetic acid). 1H NMR (300 MHz, DMSO-d6) □ 13.10 (s, 1H), 10.86 (s, 1H), 8.20 (m, 1H), 7.86 (m, 1H), 7.48 (m, 4H), 7.28 (m, 4H), 6.99 (m, 1H), 6.90 (m, 2H), 4.23 (t, 2H), 3.45 (t, 2H), 2.25 (m, 2H), 2.05 (s, 3H).

Workup

  1. extractionextracted (3×5 ml) with ethyl acetate
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. filtrationfiltered through a syringe
  6. filtrationfilter
  7. concentrationThe filtrate was concentrated
  8. customThe concentrate was purified by reverse phase HPLC (50-95% acetonitrile/water/0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-581e241377c24545ae504674323a676d
Source dataset
uspto-grants-2013_05
Patent number
US08445679B2

Reaction notes

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