Benzaldehyde → 6-(1-benzylpiperidin-3-yloxy)-2H-isoquinolin-1-one

HRID 1435992Notes

Reaction equation

HRID 1435992 reaction equation
C(O[BH-](O[C:11](=[O:13])[CH3:12])OC(=O)C)(=O)C.[Na+].ClC1C2[C:20](=[CH:21][C:22]([O:26][CH:27]3[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]3)=[CH:23][CH:24]=2)[CH:19]=[CH:18][N:17]=1.[CH:33](=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.Cl>C(O)(=O)C.CN(C)C=O>[CH2:33]([N:29]1[CH2:30][CH2:31][CH2:32][CH:27]([O:26][C:22]2[CH:21]=[C:20]3[C:12](=[CH:24][CH:23]=2)[C:11](=[O:13])[NH:17][CH:18]=[CH:19]3)[CH2:28]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 866129781-Chloro-6-(piperidin-3-yloxy)isoquinoline

Product 1

HCID 576525556-(1-benzylpiperidin-3-yloxy)-2H-isoquinolin-1-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
180 °C

Procedure

Sodium triacetoxyborohydride (100 mg, 3.9 mol eq) was added to a solution of 1-chloro-6-(piperidin-3-yloxy)isoquinoline (40mg), acetic acid (1 drops) and benzaldehyde (40 μl) in N, N-dimethylformamide (0.5 ml) and shaken for 17 hours. The reactions were quenched with water (0.5 ml) and shaken for 1 h then loaded onto a pre-acidified SCX column using methanol and eluted with 2M ammonia in methanol. The product was concentrated in vacuo to give a residue which was treated with 5M aqueous hydrochloric acid and heated in the microwave at 180° C. for 60 minutes. The mixture was concentrated in vacuo to give a residue which was purified by prep-HPLC to give 6-(1-benzylpiperidin-3-yloxy)-2H-isoquinolin-1-one, El-MS: m/z=335.7 [M+H]+.

Workup

  1. customThe reactions were quenched with water (0.5 ml)
  2. stirringshaken for 1 h
  3. washeluted with 2M ammonia in methanol
  4. concentrationThe product was concentrated in vacuo
  5. customto give a residue which
  6. concentrationThe mixture was concentrated in vacuo
  7. customto give a residue which
  8. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-0c72ba48a82f4bf588d949125aad413e
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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