Water → HCID 57635145, compound

HRID 1971088Notes

Reaction equation

HRID 1971088 reaction equation
[CH3:1][C:2]([CH3:30])([CH3:29])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:21]#[C:22][C:23]2[CH:28]=[CH:27]C=CC=2)[N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5].C1(B(O)O)CCCC=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.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>[C:21]1([C:13]2[N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][C:15]3=[C:11]([C:9]([NH:8][C@@H:3]([C:2]([CH3:1])([CH3:29])[CH3:30])[C:4]([NH:6][CH3:7])=[O:5])=[O:10])[N:12]=2)[CH2:27][CH2:28][CH2:23][CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3861343(Cyclopent-1-en-1-yl)boronic acidHCID 57635127HCID 57635127, compound

Product 1

HCID 57635145HCID 57635145, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Compound 203 (100 mg, 0.26 mmol) was dissolved in dioxane (2 mL) and cyclopentenylboronic acid (58 mg, 0.52 mmol) was added, followed by potassium carbonate (72 mg, 0.52 mmol) and water (0.40 mL). The resulting solution was degassed with nitrogen gas and Pd(PPh3)4 (18 mg, 0.016 mmol) was added. The mixture was heated at 100° C. for 1 h under nitrogen. The organic layer was separated, solid NaCl was added and the mixture was extracted with ethyl acetate. The combined organic layers were filtered through PL-Thiol MP SPE tube to remove palladium catalyst. The filtrate was concentrated and then purified by prep LC/MS using 5-95% acetonitrile in water with 0.1% formic acid. The formic acid was removed using Strata SCX SPE tube to give a desired product (Compound 238) as a free base (81 mg, 82%). 1H-NMR (400 MHz, CDCl3) δ: 1.09 (s, 9H), 1.90-2.05 (m, 2H), 2.51 (s, 3H), 2.55-2.65 (m, 2H), 2.74-2.95 (m, 7H), 3.88-4.14 (m, 4H), 5.95 (s, 1H), 6.09 (m, 1H), 7.66 (d, 1H). LCMS (+ESI) m/z 374.2 [M+H]+.

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. additionsolid NaCl was added
  4. extractionthe mixture was extracted with ethyl acetate
  5. filtrationThe combined organic layers were filtered through PL-Thiol MP SPE tube
  6. customto remove palladium catalyst
  7. concentrationThe filtrate was concentrated
  8. custompurified by prep LC/MS
  9. customThe formic acid was removed

Sources & evidence

ORD record
ord-1c95e78ed8fa42959f048c31da372b3d
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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