Sodium triacetoxyborohydride → (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethyl benzoate

HRID 1694578Notes

Reaction equation

HRID 1694578 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]2[C:8]3[CH:9]=[CH:10][N:11]=[CH:12][C:13]=3[CH:14]=[CH:15][CH:16]=2)[CH2:2]1.[C:17]([O:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]=O)[CH:30]=1)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[C:17]([O:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][N:1]2[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:8]=3[CH:9]=[CH:10][N:11]=[CH:12]4)[CH2:2]2)[CH:30]=1)(=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 44594455(R)-N-(pyrrolidin-3-yl)isoquinolin-5-amineHCID 445944592-(3-Formylphenoxy)ethyl benzoate

Product 1

HCID 44594600(R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethyl benzoateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

To a 100 mL round-bottomed flask with a magnetic stir bar were added (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine scuccinic acid salt (2.00 g, 6.04 mmol, from Example 5), tetrahydrofuran (30 mL), and 2-(3-formylphenoxy)ethyl benzoate (1.63 g, 6.04 mmol). The mixture was stirred at 20 to 25° C. for 15 minutes. To the mixture was added sodium triacetoxyborohydride (1.92 g, 9.05 mmol). The mixture was stirred at 20 to 25° C. for 20 hours. The reaction was quenched with 20 mL of 15% Na2CO3 (final pH ˜10). Tetrahydrofuran was removed by distillation under vacuum. The residue was extracted with 30 mL of methyl tert-butyl ether. The organic layer was washed with 30 mL of water (twice) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-12% methanol/dichloromethane) to give (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethyl benzoate as a oil (2.57 g, 91% yield).

Workup

  1. stirringThe mixture was stirred at 20 to 25° C. for 20 hours
  2. customThe reaction was quenched with 20 mL of 15% Na2CO3 (final pH ˜10)
  3. customTetrahydrofuran was removed by distillation under vacuum
  4. extractionThe residue was extracted with 30 mL of methyl tert-butyl ether
  5. washThe organic layer was washed with 30 mL of water (twice) and
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-12% methanol/dichloromethane)

Sources & evidence

ORD record
ord-ed35e0640d224317bdbec9b861b8a4ce
Source dataset
uspto-grants-2012_04
Patent number
US08158796B2

Reaction notes

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