Sodium Carbonate → HCID 178502379, compound

HRID 1776030Notes

Reaction equation

HRID 1776030 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][O:8][C:9](=[O:42])[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](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:28]=2)[N:26]=1)=[O:16])[CH:12]([CH3:14])[CH3:13].Br[C:44]1[CH:50]=[CH:49][C:47]([NH2:48])=[CH:46][C:45]=1[Cl:51]>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.O>[CH3:7][O:8][C:9](=[O:42])[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:28]=[CH:29][C:30]([C:44]3[CH:50]=[CH:49][C:47]([NH2:48])=[CH:46][C:45]=3[Cl:51])=[CH:31][CH:32]=2)[N:26]=1)=[O:16])[CH:12]([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 888884-Bromo-3-chloroanilineHCID 178502353HCID 178502353, compound

Product 1

HCID 178502379HCID 178502379, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Saturated aqueous sodium carbonate (0.2 mL) was added to a mixture of [(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 (100 mg, 0.20 mmol), 4-bromo-3-chloroaniline (46 mg, 0.22 mmol), tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.02 mmol), and water (0.3 mL). The reaction mixture was purged with nitrogen and then 1,4-dioxane (0.7 mL) was added. The reaction mixture was degassed, stirred, and heated at 90° C. overnight. Water and ethyl acetate were added; the reaction mixture was concentrated; dissolved in 1:1 acetic acid:water (1 mL) and purified by preparative HPLC. Fractions were combined, adjusted to pH 8-9 with aqueous sodium bicarbonate, and extracted with DCM. Extracts were washed with water, dried with sodium sulfate, and concentrated. The concentrate was dissolved in methanol and concentrated under vacuum to provide the title compound (m/z): [M+H]+ calcd for C26H30ClN5O3 496.20 found 496.7.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. addition1,4-dioxane (0.7 mL) was added
  3. customThe reaction mixture was degassed
  4. additionWater and ethyl acetate were added
  5. concentrationthe reaction mixture was concentrated
  6. dissolutiondissolved in 1:1 acetic acid
  7. customwater (1 mL) and purified by preparative HPLC
  8. extractionextracted with DCM
  9. washExtracts were washed with water
  10. dry with materialdried with sodium sulfate
  11. concentrationconcentrated
  12. dissolutionThe concentrate was dissolved in methanol
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-eeca1eee35d64686a958774ac2a5eff8
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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