Sodium triacetoxyborohydride → HCID 18409581, compound

HRID 993153Notes

Reaction equation

HRID 993153 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([CH:6]=O)=[N:2]1.[NH2:8][C:9]([CH3:31])([CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1)[C:10]([NH:12][CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:14])=[O:11].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>N1C=CC=CC=1>[NH:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:22]([CH2:21][C:9]([CH3:31])([NH:8][CH2:6][C:3]2[NH:2][N:1]=[CH:5][CH:4]=2)[C:10]([NH:12][CH:13]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:14])=[O:11])=[CH:23]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydride2×HCID 122183831H-Pyrazole-3-carbaldehydeHCID 18409735HCID 18409735, compound

Product 1

HCID 18409581HCID 18409581, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

To a stirred solution of pyrazole-3-carboxaldehyde (96 mg, 1 mmol, supplied as dimer) in pyridine (10 mL) was added 2-amino-3-(1H-indol-3-yl)-2-methyl-N-(1-phenyl-ethyl)-propionamide (161 mg, 0.5 mmol) followed by sodium triacetoxyborohydride (848 mg, 4 mmol). After stirring over night at room temperature another portion of sodium triacetoxyborohydride (424 mg, 2 mmol) was added. After stirring over night at room temperature the pyridine was removed under reduced pressure. The residue was taken up in CH2Cl2 (100 mL) and saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 (100 mL). The combined organic phases were washed with brine (50 mL), dried (MgSO4), and the solvent was removed under reduced pressure. The residue was initially purified by chromatography on normal phase silica using 95% EtOAc in heptane as eluent. The solvent was removed under reduced pressure and the residue was dissolved in aqueous acetonitrile and acidified using formic acid. Purification by chromatography on reverse phase silica using 25% CH3CN in H2O (0.1% formic acid in mobile phases) as eluent gave pure product. The solvent was removed under reduced pressure and the residue was suspended between EtOAc and saturated NaHCO3. The EtOAc was dried (MgSO4) and the solvent was removed under reduced pressure to give pure product as a glass (20 mg, 10%); IR (film): 3260, 3059, 2979, 2927, 1651, 1515, 1456, 1374, 1266, 1105, 1048, 1011, 932, 741 cm−1; NMR (DMSO-d6): δ1.22 (3H, s); 1.35 (3H, d, J=6.8 Hz); 2.26 (1H, s); 2.96-3.05 (2H, m); 3.50-3.75 (2H, m); 4.93 (1H, s); 6.10 (1H, s); 6.89-6.93 (2H, m); 7.00-7,04 (1H, m); 7.18-7.32 (6H, m); 7.35 (0.5H, s); 7.52 (1H, d, J=7.8 Hz); 7.60 (0.5H, s); 8.05-8.20 (1H, m); 10.82 (1H, s); 12.52 (0.5H, s); 12.73 (0.5H, s); MS m/e (ES+): 424.1 (27%); 402.1 (100%, M++H).

Workup

  1. additionwas added
  2. customwas removed under reduced pressure
  3. extractionThe aqueous phase was extracted with CH2Cl2 (100 mL)
  4. washThe combined organic phases were washed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was initially purified by chromatography on normal phase silica using 95% EtOAc in heptane as eluent
  8. customThe solvent was removed under reduced pressure
  9. dissolutionthe residue was dissolved in aqueous acetonitrile
  10. customPurification by chromatography on reverse phase silica using 25% CH3CN in H2O (0.1% formic acid in mobile phases) as eluent
  11. customgave pure product
  12. customThe solvent was removed under reduced pressure
  13. dry with materialThe EtOAc was dried (MgSO4)
  14. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-63a056a329054736ad5dc19e95b85f6c
Source dataset
uspto-grants-2002_10
Patent number
US06472418B1

Reaction notes

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