Acetic Acid → 6-{1-[(3-Methylbutylamino)methyl]isoquinolin-4-yloxy}nicotinamide

HRID 2060899Notes

Reaction equation

HRID 2060899 reaction equation
[CH:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][N:15]=2)=[CH:5][N:4]=1)=O.[CH3:23][CH:24]([CH3:28])[CH2:25][CH2:26][NH2:27].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+]>ClC(Cl)C>[CH3:23][CH:24]([CH3:28])[CH2:25][CH2:26][NH:27][CH2:1][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][N:15]=2)=[CH:5][N:4]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7894IsoamylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 594013146-(1-Formylisoquinolin-4-yloxy)nicotinamide

Product 1

HCID 251214806-{1-[(3-Methylbutylamino)methyl]isoquinolin-4-yloxy}nicotinamide

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To 6-(1-formylisoquinolin-4-yloxy)nicotinamide (Preparation 20) (130 mg, 0.44 mmol) in dichloroethane (8 mL) was added 3-methylbutylamine (154 μL, 1.33 mmol), NaBH(OAc)3 (282 mg, 1.33 mmol) and acetic acid (76 μL, 1.33 mmol). The mixture was stirred for 16 h. NaHCO3 (50 mL) was added and the mixture extracted with EtOAc (3×40 mL). The organic phase was washed with water (30 mL), brine (30 mL) and dried (MgSO4). Solvent was removed in vacuo and the residue purified by column chromatography (0.5 NH3: 5 MeOH: 95 DCM) to give the title compound: RT=2.48 min; m/z (ES+)=365.2 [M+H]+.

Workup

  1. extractionthe mixture extracted with EtOAc (3×40 mL)
  2. washThe organic phase was washed with water (30 mL), brine (30 mL)
  3. dry with materialdried (MgSO4)
  4. customSolvent was removed in vacuo
  5. customthe residue purified by column chromatography (0.5 NH3: 5 MeOH: 95 DCM)

Sources & evidence

ORD record
ord-130144816ffc4650bbc2d6510b1d6fee
Source dataset
uspto-grants-2012_10
Patent number
US08278442B2

Reaction notes

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