Acetic Acid → HCID 44242760, compound

HRID 657431Notes

Reaction equation

HRID 657431 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].[CH:44]12[CH2:50][CH:47]([NH:48][CH2:49]1)[CH2:46][N:45]2C(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>[CH:44]12[CH2:50][CH:47]([NH:48][CH2:49]1)[CH2:46][N:45]2[CH2:39][C:35]1[CH:34]=[C:33]([C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([CH2:26][NH:25][C:23](=[O:24])[CH2:22][C:21]([NH:20][CH2:19][C:10]3[C:11]([NH:12][CH:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[C:6]4[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]4=[N:8][C:9]=3[CH2:42][CH3:43])=[O:41])[CH:28]=2)[CH:38]=[CH:37][CH:36]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 2760898(1S,4S)-tert-butyl 2,5-diazabicyclo(2.2.1)heptane-2-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 57819888HCID 57819888, compound

Product 1

HCID 44242760HCID 44242760, compoundYield 11.5%

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 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (34 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 the solvent evaporated using a GeneVac EZ-2 evaporator. To the resulting residue was added TFA (0.198 mL, 2.57 mmol) in dichloromethane (0.2 mL) and the 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 the solvent evaporated using a GeneVac EZ-2 evaporator, basified by amine cartridge to afford the title compound 6.6 mg (11%). LC-MS m/z 665 (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. customthe solvent evaporated
  9. customa GeneVac EZ-2 evaporator
  10. customthe mixture was placed in a Glas-Col evaporator overnight
  11. dissolutionthe residue was redissolved in MeOH/DMSO
  12. custompurified
  13. customthe solvent evaporated
  14. customa GeneVac EZ-2 evaporator

Sources & evidence

ORD record
ord-0e8c49485d6244aea0fa87691a825e58
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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