Acetic Acid → HCID 44242758, compound

HRID 657429Notes

Reaction equation

HRID 657429 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:42][CH3:43])=[C:10]([CH2:19][NH:20][C:21](=[O:41])[CH2:22][C:23]([NH:25][CH2:26][C:27]3[CH:28]=[C:29]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([CH:39]=O)[CH:34]=4)[CH:30]=[CH:31][CH:32]=3)=[O:24])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[CH3:44][C@@H:45]1[CH2:50][NH:49][CH2:48][CH2:47][N:46]1C(OC(C)(C)C)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O.C(O)(C(F)(F)F)=O>CS(C)=O.ClCCl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:42][CH3:43])=[C:10]([CH2:19][NH:20][C:21](=[O:41])[CH2:22][C:23]([NH:25][CH2:26][C:27]3[CH:28]=[C:29]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39][N:49]5[CH2:48][CH2:47][NH:46][C@H:45]([CH3:44])[CH2:50]5)[CH:34]=4)[CH:30]=[CH:31][CH:32]=3)=[O:24])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 57819888HCID 57819888, compound

Product 1

HCID 44242758HCID 44242758, compoundYield 9.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-3-biphenylyl)methyl]propanediamide (50 mg, 0.086 mmol) was added 1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate (34.4 mg, 0.172 mmol) followed by NaB(OAc)3H (36.4 mg, 0.172 mmol) and AcOH (4.91 μL, 0.086 mmol) in dimethyl sulfoxide (DMSO) (0.5 mL). The mixture was stirred overnight at room temperature. The reaction was quenched with saturated NaHCO3 and extracted with EtOAc (3×1 mL). Combined organic layers were washed with saturated NaCl, dried (Na2SO4) and concentrated. The crude products were redissolved in MeOH/DMSO (1/1) and purified using a Gilson HPLC (acidic condition). Product fractions were combined and solvent evaporated using a GeneVac EZ-2 evaporator. To the obtained residue was added TFA (0.198 mL, 2.57 mmol) in dichloromethane (0.2 mL) and that mixture was placed in a Glas-Col evaporator overnight and then the residue was redissolved in MeOH/DMSO and purified using a Gilson HPLC (acidic condition). Product fractions were combined and solvent was evaporated using a GeneVac EZ-2 evaporator That residue was basified by cartridge to afford the title compound 5.7 mg (9.4%). LC-MS m/z 667 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated NaHCO3
  2. extractionextracted with EtOAc (3×1 mL)
  3. washCombined organic layers were washed with saturated NaCl
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe crude products were redissolved in MeOH/DMSO (1/1)
  7. custompurified
  8. customsolvent evaporated
  9. customa GeneVac EZ-2 evaporator
  10. customthat mixture was placed in a Glas-Col evaporator overnight
  11. dissolutionthe residue was redissolved in MeOH/DMSO
  12. custompurified
  13. customsolvent was evaporated
  14. customa GeneVac EZ-2 evaporator That residue

Sources & evidence

ORD record
ord-53dedc995e2d453795dd9f1af7c0b054
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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