Acetic Acid → HCID 67995329, compound

HRID 2361325Notes

Reaction equation

HRID 2361325 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([N:21]5[CH2:29][C:28]6[C:23](=[CH:24][C:25]([Cl:30])=[CH:26][CH:27]=6)[C:22]5=[O:31])[C:16]=4[CH3:32])=[CH:13][N:12]=[C:11]([C:33]([NH2:35])=[O:34])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[O:36]1[CH2:40][CH2:39][C:38](=O)[CH2:37]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C1COCC1.CS(C)=O.CO.O.CCOC(C)=O>[Cl:30][C:25]1[CH:24]=[C:23]2[C:28]([CH2:29][N:21]([C:17]3[C:16]([CH3:32])=[C:15]([C:14]4[C:6]5[C:5]6[C:9](=[CH:10][C:2]([NH:1][CH:38]7[CH2:39][CH2:40][O:36][CH2:37]7)=[CH:3][CH:4]=6)[NH:8][C:7]=5[C:11]([C:33]([NH2:35])=[O:34])=[N:12][CH:13]=4)[CH:20]=[CH:19][CH:18]=3)[C:22]2=[O:31])=[CH:27][CH:26]=1

Participants

11

Reactant 4

HCID 176Acetic AcidHCID 5293923-OxotetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 67994825HCID 67994825, compound

Product 1

HCID 67995329HCID 67995329, compoundYield 2.8%

Reagents, catalysts & solvents 6

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a light burgundy, homogeneous solution of 7-amino-4-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.0695 g, 0.144 mmol), dihydrofuran-3(2H)-one (0.050 g, 0.577 mmol) and acetic acid (0.041 mL, 0.721 mmol) in dichloromethane (1.602 mL) and THF (1.602 mL) was added sodium triacetoxyborohydride (0.122 g, 0.577 mmol). The reaction was stirred overnight. Water (2 mL) was added, and the solution was stirred at room temperature for 10 min. EtOAc (50 mL) and water (20 mL) were added. After separation of layers, the organic layer was washed with sat. aq. NaHCO3, brine (20 mL), dried over MgSO4, and concentrated in vacuo to give a residue which was diluted with DMSO (0.2 mL) and MeOH (0.8 mL) and purified by reverse phase HPLC. The appropriate fractions were collected, basified with NaHCO3 (solid), and concentrated in vacuo. The residue was extracted with CH2Cl2 (3×). The combined extract was dried over Na2SO4 and concentrated in vacuo to give the desired product (0.00234 g, 4.03 μmol, 2.79% yield) as a tan solid. LC/MS (M+H)=552.24.

Workup

  1. stirringthe solution was stirred at room temperature for 10 min
  2. customAfter separation of layers
  3. washthe organic layer was washed with sat. aq. NaHCO3, brine (20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give a residue which
  7. custompurified by reverse phase HPLC
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated in vacuo
  10. extractionThe residue was extracted with CH2Cl2 (3×)
  11. extractionThe combined extract
  12. dry with materialwas dried over Na2SO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d120125e91b540c7b615aeb1f56ba0a7
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…