Water → HCID 178502378, compound

HRID 1776026Notes

Reaction equation

HRID 1776026 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:35])[NH:10][C@H:11]([C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]1[NH:23][CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][C:30](Br)=[C:29]([CH3:34])[CH:28]=2)[N:26]=1)=[O:16])[CH:12]([CH3:14])[CH3:13].[CH3:36][C:37]1[CH:38]=[C:39]([NH2:52])[CH:40]=[CH:41][C:42]=1B1OC(C)(C)C(C)(C)O1.C1(C)C=CC=CC=1.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:7][O:8][C:9](=[O:35])[NH:10][C@H:11]([C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]1[NH:23][CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([C:42]3[CH:41]=[CH:40][C:39]([NH2:52])=[CH:38][C:37]=3[CH3:36])=[C:29]([CH3:34])[CH:28]=2)[N:26]=1)=[O:16])[CH:12]([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 962WaterHCID 1140TolueneHCID 11430Potassium CarbonateHCID 177502103-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 178502355HCID 178502355, compound

Product 1

HCID 178502378HCID 178502378, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

Potassium carbonate (224 mg, 1.619 mmol) was added to a mixture of ((S)-1-{(S)-2-[4-(4-bromo-3-methyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (150 mg, 0.324 mmol) and 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (90.6 mg, 0.389 mmol) in toluene (0.6 mL, 6 mmol) and water (0.3 mL, 20 mmol). The reaction mixture was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (44.9 mg, 0.039 mmol) was added under nitrogen and then the reaction mixture was capped and heated at 100° C. overnight, cooled to RT and partitioned between ethyl acetate (10 mL) and water (2 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to give a brownish 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 compound as a light yellowish foam (135 mg, 85% yield). (m/z): [M+H]+ calcd for C28H35N5O3 490.27 found 490.6.

Workup

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

Sources & evidence

ORD record
ord-19eddfd936dd412093e0d5b1815d268b
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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