Acetic Acid → HCID 44242759, compound

HRID 657430Notes

Reaction equation

HRID 657430 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].[NH:44]1[CH2:48][CH2:47][C@H:46]([NH:49]C(=O)OC(C)(C)C)[CH2:45]1.[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>[NH2:49][C@H:46]1[CH2:47][CH2:48][N:44]([CH2:39][C:35]2[CH:34]=[C:33]([C:29]3[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]4[C:11]([NH:12][CH:13]5[CH2:18][CH2:17][O:16][CH2:15][CH2:14]5)=[C:6]5[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]5=[N:8][C:9]=4[CH2:42][CH3:43])=[O:41])[CH:28]=3)[CH:38]=[CH:37][CH:36]=2)[CH2:45]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 57819888HCID 57819888, compound

Product 1

HCID 44242759HCID 44242759, compoundYield 11.2%

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 (3S)-3-pyrrolidinylcarbamate (32 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). The 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 the Glas-Col evaporator overnight. The resulting 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, and basified by amine cartridge to afford the title compound 6.3 mg (11%). LC-MS m/z 653 (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 the Glas-Col evaporator overnight
  11. dissolutionThe resulting residue was redissolved in MeOH/DMSO
  12. custompurified
  13. customthe solvent evaporated
  14. customa GeneVac EZ-2 evaporator

Sources & evidence

ORD record
ord-44cd018a7ea14ce18cbcbe1ef5b2908e
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

Loading…