Triethylamine → rac-5-cyclopropyl-2-(trans-2-hydroxycyclopentyl)-6-(4-(1H-pyrazol-1-yl)benzyl)isoindolin-1-one

HRID 629353Notes

Reaction equation

HRID 629353 reaction equation
[N:1]1([C:6]2[CH:27]=[CH:26][C:9]([CH2:10][C:11]3[C:12]([CH:23]4[CH2:25][CH2:24]4)=[CH:13][C:14]([CH:21]=O)=[C:15]([CH:20]=3)[C:16](OC)=[O:17])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.Cl.[NH2:29][C@@H:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[OH:35].C(N(CC)CC)C.S([O-])([O-])(=O)=O.[Mg+2]>C1COCC1>[CH:23]1([C:12]2[CH:13]=[C:14]3[C:15](=[CH:20][C:11]=2[CH2:10][C:9]2[CH:26]=[CH:27][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:7][CH:8]=2)[C:16](=[O:17])[N:29]([C@@H:30]2[CH2:34][CH2:33][CH2:32][C@H:31]2[OH:35])[CH2:21]3)[CH2:24][CH2:25]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 12886906(1R,2R)-2-aminocyclopentan-1-ol hydrochlorideHCID 118468291methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-4-cyclopropyl-2-formylbenzoate

Product 1

HCID 118468397rac-5-cyclopropyl-2-(trans-2-hydroxycyclopentyl)-6-(4-(1H-pyrazol-1-yl)benzyl)isoindolin-1-oneYield 49.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-4-cyclopropyl-2-formylbenzoate (0.11 g), trans-2-aminocyclopentanol hydrochloride (0.04 g), triethylamine (0.04 mL) and anhydrous magnesium sulfate (0.07 g) in THF (2.20 mL) was stirred at room temperature for 5 hr. The insoluble substance was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was diluted with methanol (2.20 mL) and THF (2.20 mL), sodium triacetoxyborohydride (0.13 g) was added thereto, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.06 g).

Workup

  1. customThe insoluble substance was removed by filtration
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionThe residue was diluted with methanol (2.20 mL) and THF (2.20 mL), sodium triacetoxyborohydride (0.13 g)
  4. additionwas added
  5. additionThe reaction mixture was diluted with ethyl acetate
  6. washthe mixture was washed with water and saturated brine
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cb17338163114bbc8d3c8e124c59513d
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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