Sodium borohydride → 7-(1-Hydroxyethyl)-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361371Notes

Reaction equation

HRID 2361371 reaction equation
[C:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[CH2:31][C:30]6[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][CH:29]=6)[C:24]5=[O:34])[C:18]=4[CH3:35])=[CH:15][N:14]=[C:13]([C:36]([NH2:38])=[O:37])[C:9]=3[NH:10]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>O1CCCC1.CO>[OH:3][CH:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[CH2:31][C:30]6[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][CH:29]=6)[C:24]5=[O:34])[C:18]=4[CH3:35])=[CH:15][N:14]=[C:13]([C:36]([NH2:38])=[O:37])[C:9]=3[NH:10]2)=[CH:6][CH:5]=1)[CH3:2]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 679946867-Acetyl-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 706519757-(1-Hydroxyethyl)-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 38.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cloudy solution of 7-acetyl-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (62 mg, 0.123 mmol) in tetrahydrofuran (5 mL) and methanol (15 mL) at 0° C. was added sodium borohydride (23.25 mg, 0.614 mmol) in one portion. The mixture was stirred at room temperature for 30 min and then the reaction was quenched with ice cold water (15 mL). The resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum, and the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with dichloromethane (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (24.8 mg, 0.047 mmol, 38.6% yield) as a white solid. LCMS (M+H)+=507.24. 1H NMR (500 MHz, DMSO-d6) δ: 11.77 (s, 1H), 8.32 (s, 1H), 8.23 (s, 1H), 7.83 (d, J=11.6 Hz, 1H), 7.75 (s, 1H), 7.67 (d, J=6.9 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.54 (m, 1H), 7.43 (d, J=7.5 Hz, 1H), 7.32 (m, 1H), 7.27-7.23 (m, 2H), 7.08 (dd, J1=12.9 Hz, J2=8.5 Hz, 1H), 5.26 (m, 1H), 4.85 (m, 1H), 4.96 (d, J=16.9 Hz, 1H), 4.86 (d, J=16.9 Hz, 1H), 3.86 (s, 3H), 1.88 (s, 3H), 1.38 (d, J=6.4 Hz, 3H).

Workup

  1. customthe reaction was quenched with ice cold water (15 mL)
  2. extractionThe resulting mixture was extracted with ethyl acetate (3×30 mL)
  3. extractionThe combined extract
  4. washwas washed with brine (25 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationThe organic solution was concentrated under vacuum
  7. customthe residue was purified by reverse phase HPLC
  8. concentrationThe correct fraction was concentrated under vacuum
  9. extractionextracted with dichloromethane (3×35 mL)
  10. extractionThe combined extract
  11. washwas washed with brine (30 mL)
  12. dry with materialdried over anhydrous MgSO4
  13. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-5ef0397bc57a488b9edb323334ef6c42
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…