Acetic Acid → HCID 70980589, compound

HRID 1520237Notes

Reaction equation

HRID 1520237 reaction equation
Cl.[CH:2]1[C:11]2[C:6](=[C:7]([NH:12][CH:13]3[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]3)[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[O-]S([O-])(=O)=O.[Mg+2].[CH:32]([C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=1)[C:37]([OH:39])=[O:38])=O.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CO.C(Cl)Cl>[CH:2]1[C:11]2[C:6](=[C:7]([NH:12][CH:13]3[CH2:18][CH2:17][CH2:16][N:15]([CH2:32][C:34]4[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=4)[C:37]([OH:39])=[O:38])[CH2:14]3)[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 120773-CarboxybenzaldehydeHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5049666Sodium triacetoxyborohydrideHCID 69523874N-(Piperidin-3-yl)isoquinolin-5-amine--hydrogen chloride (1/1)

Product 1

HCID 70980589HCID 70980589, compoundYield 74.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of Intermediate 4 (10 g×2, 0.0379 mol×2) in DCE (400 mL×2) was added Et3N (9.2 g×2, 0.0910 mol×2) and MgSO4 (20×2, 0.139 mol×2), and stirred for 0.5 h at 30° C. 3-formylbenzoic acid (6.26 g×2, 0.0417 mol×2) and AcOH (5.46 g×2, 0.0910 mol×2) was added. The reaction mixture was stirred at 30° C. for 0.5 hours. NaBH(OAc)3 (24.1 g×2, 0.1137 mol×2) was added and the reaction mixture was stirred at 30° C. overnight. TLC (methylene dichloride:methanol=10:1) showed the reaction was complete. The reaction mixture was filtered. The filtered cake was washed with CH2Cl2, the filtrate was washed with brine, dried over Na2SO4 and concentrated in vacuo, and purified by preparative HPLC to give Intermediate 5 (10.2 g, 37.2%) as a yellow solid.

Workup

  1. stirringThe reaction mixture was stirred at 30° C. for 0.5 hours
  2. stirringthe reaction mixture was stirred at 30° C. overnight
  3. filtrationThe reaction mixture was filtered
  4. washThe filtered cake was washed with CH2Cl2
  5. washthe filtrate was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-79f6d6892ee54dd4b11656131fe20c12
Source dataset
uspto-grants-2015_07
Patent number
US09073905B2

Reaction notes

Loading…