Acetic Acid → HCID 45137698, compound

HRID 559652Notes

Reaction equation

HRID 559652 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[C:9]([C@@H:11]([NH:15][C:16]([C:18]2[C:19]3[CH:26]=[N:25][N:24]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[C:20]=3[CH:21]=[N:22][CH:23]=2)=[O:17])[CH2:12][CH:13]=O)[CH:8]=[CH:7][N:6]=1)(=[O:4])=[O:3].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:1][S:2]([C:5]1[CH:10]=[C:9]([C@@H:11]([NH:15][C:16]([C:18]2[C:19]3[CH:26]=[N:25][N:24]([C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)[C:20]=3[CH:21]=[N:22][CH:23]=2)=[O:17])[CH2:12][CH2:13][N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)[CH:8]=[CH:7][N:6]=1)(=[O:4])=[O:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 59278338HCID 59278338, compound

Product 1

HCID 45137698HCID 45137698, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[(S)-1-(2-methanesulfonyl-pyridin-4-yl)-3-oxo-propyl]-amide (40 mg, 0.09 mmol) and morpholine (15 μL, 0.17 mmol) in dichloroethane (2 mL) was stirred for 30 minutes. The mixture was then acidified (pH=4) with acetic acid (9 μL, 0.2 mmol) and then sodium triacetoxyborohydride (36 mg, 0.17 mmol) was added. After 2 hours, the reaction was quenched with saturated aqueous sodium bicarbonate (20 mL) and extracted with dichloromethane (3×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The oily residue was purified by silica gel chromatography using a gradient of 0-10% methanol in EtOAc. The solid material from the column was purified a second time by reversed-phase HPLC using a 20 minute gradient of 5-95% MeCN (0.1% TFA) in H2O (0.1% TFA) (flow rate=25 mL/minute). Desired fractions from the column was made basic with saturated aqueous sodium bicarbonate (2 mL), concentrated to half of the original volume and extracted with EtOAc (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to afford the title compound as a white solid.

Workup

  1. customthe reaction was quenched with saturated aqueous sodium bicarbonate (20 mL)
  2. extractionextracted with dichloromethane (3×20 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe oily residue was purified by silica gel chromatography
  7. customThe solid material from the column was purified a second time by reversed-phase
  8. waitHPLC using a 20 minute
  9. concentrationconcentrated to half of the original volume
  10. extractionextracted with EtOAc (3×10 mL)
  11. dry with materialThe combined organic layers were dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-4efe404f11b846469e0853691f4d2035
Source dataset
uspto-grants-2011_11
Patent number
US08063065B2

Reaction notes

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