Water → HCID 178502394, compound

HRID 1776032Notes

Reaction equation

HRID 1776032 reaction equation
Br[C:2]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.[CH3:14][O:15][C:16](=[O:49])[NH:17][C@H:18]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[N:33]=1)=[O:23])[CH:19]([CH3:21])[CH3:20].C1(C)C=CC=CC=1.O.C(=O)([O-])[O-].[K+].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:14][O:15][C:16](=[O:49])[NH:17][C@H:18]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:35]=[CH:36][C:37]([C:2]3[CH:3]=[C:4]([F:13])[C:5]([NH2:6])=[CH:7][C:8]=3[C:9]([F:12])([F:11])[F:10])=[CH:38][CH:39]=2)[N:33]=1)=[O:23])[CH:19]([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 962WaterHCID 1140TolueneHCID 11430Potassium CarbonateHCID 70180464-Bromo-2-fluoro-5-(trifluoromethyl)anilineHCID 178502353HCID 178502353, compound

Product 1

HCID 178502394HCID 178502394, compoundYield 77.4%

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 4-bromo-2-fluoro-5-(trifluoromethyl)aniline (78 mg, 0.302 mmol) and [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (150 mg, 0.302 mmol) in toluene (0.6 mL, 6 mmol) and water (0.4 mL, 20 mmol) was purged with nitrogen. Potassium carbonate (208.8 g, 1.511 mmol) and tetrakis(triphenylphosphine)-palladium(0) (35 mg, 0.030 mmol) were added under an atmosphere of nitrogen. The reaction mixture was capped and heated at 100° C. overnight, cooled to RT, and partitioned between ethyl acetate (5.0 mL) and water (1.5 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated to give a yellowish oil, which was purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes). Desired fractions were combined and concentrated to give the title intermediate as a yellowish solid (128 mg, 77% yield). (m/z): [M+H]+ calcd for C27H24F4N5O3 548.22 found 548.6.

Workup

  1. customwas purged with nitrogen
  2. customThe reaction mixture was capped
  3. temperaturecooled to RT
  4. custompartitioned between ethyl acetate (5.0 mL) and water (1.5 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellowish oil, which
  9. customwas purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-2861e47cb01b429aa17def51b4713823
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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