2,2'-Oxybisacetaldehyde → 7-methoxy-3-(4-methoxyphenyl)-4-morpholinoisoquinolin-1(2H)-one

HRID 333676Notes

Reaction equation

HRID 333676 reaction equation
[CH2:1]1[O:7][CH2:6][C@@H:4](O)[C@H:2]1O.[NH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[C:12](=[O:21])[NH:11][C:10]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1.[BH3-]C#N.[Na+].O(CC=O)CC=O>O.CC#N.C(O)(=O)C.O>[CH3:20][O:19][C:15]1[CH:14]=[C:13]2[C:18]([C:9]([N:8]3[CH2:2][CH2:1][O:7][CH2:6][CH2:4]3)=[C:10]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[NH:11][C:12]2=[O:21])=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 819582,2'-OxybisacetaldehydeHCID 6417731,4-AnhydroerythritolHCID 5003444Sodium cyanoborohydrideHCID 533806664-amino-7-methoxy-3-(4-methoxyphenyl)isoquinolin-1(2H)-one2×

Product 1

HCID 533794737-methoxy-3-(4-methoxyphenyl)-4-morpholinoisoquinolin-1(2H)-oneYield 8.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 962WaterSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

NaIO4 (66 mg, 0.33 mmol) is added to a flask containing 1,4-anhydroerythritol (34 mg, 0.33 mmol) dissolved in a water/CH3CN mixture (1:1; 4 mL) and the mixture is maintained under stirring for 18 hours. 4-amino-7-methoxy-3-(4-methoxyphenyl)isoquinolin-1(2H)-one (compound 1) (100 mg, 0.33 mmol) and NaBH3CN (63 mg, 1 mmol) are then added to the solution of 2,2′-oxybis(acetaldehyde) prepared previously. Then, 3 drops of acetic acid are added and the medium is stirred for 3 hours at ambient temperature. The reaction is stopped by the addition of 10 mL of water. The medium is extracted with 3×10 mL of dichloromethane. The organic phases are washed with 3×10 mL of water, dried over MgSO4 and concentrated under vacuum. The residue is purified by silica gel column chromatography with dichloromethane-ethanol (100/0 to 98/2) as eluent in order to produce successively i) the compound 7-methoxy-3-(4-methoxyphenyl)-4-morpholinoisoquinolin-1(2H)-one 49 (10 mg, 8%) in the form of a white solid, mp>270° C.; 1H NMR (CDCl3): 8.18 (1H, br s), 7.99 (1H, d), 7.83 (1H, dd), 7.37 (3H, m), 7.03 (2H, d), 3.97 (3H, s), 3.91 (3H, s), 3.72 (4H, m), 2.90 (2H, m), 2.75 (2H, m); MS 367 (M+H); and ii) the compound 4-(2-(2-hydroxyethoxy)ethylamino)-7-methoxy-3-(4-methoxyphenyl)isoquinolin-1(2H)-one 50 (15 mg, 12%) in the form of a white solid, mp 139° C.; 1H NMR (CDCl3): 8.71 (1H, br s), 7.89 (1H, d), 7.82 (1H, s), 7.45 (2H, d), 7.34 (1H, dd), 7.01 (2H, d), 3.94 (3H, s), 3.87 (3H, s), 3.60 (2H, t), 3.49 (2H, t), 3.38 (2H, t), 3.03 (2H, t), 1.75 (1H, br s), MS 385 (M+H).

Workup

  1. temperaturethe mixture is maintained
  2. customprepared previously
  3. stirringthe medium is stirred for 3 hours at ambient temperature
  4. extractionThe medium is extracted with 3×10 mL of dichloromethane
  5. washThe organic phases are washed with 3×10 mL of water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under vacuum
  8. customThe residue is purified by silica gel column chromatography with dichloromethane-ethanol (100/0 to 98/2) as eluent in order

Sources & evidence

ORD record
ord-b07da1bb9d5a4d80b7a49e9741862d80
Source dataset
uspto-grants-2014_11
Patent number
US08883763B2

Reaction notes

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