Acetic Acid → HCID 44242693, compound

HRID 657428Notes

Reaction equation

HRID 657428 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](C=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].[N:44]1([C:51](OC(C)(C)C)=O)[CH2:50][CH2:49][CH2:48][NH:47][CH2:46][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>[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:34]=[CH:35][CH:36]=[C:37]([CH2:51][N:44]5[CH2:50][CH2:49][CH2:48][NH:47][CH2:46][CH2:45]5)[CH:38]=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 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 57819888HCID 57819888, compound

Product 1

HCID 44242693HCID 44242693, compoundYield 14.6%

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 hexahydro-1H-1,4-diazepine-1-carboxylate (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 conditions) and solvent evaporated using a GeneVac EZ-2 evaporator. To this material 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. The resultant residue was then redissolved in MeOH/DMSO and purified using a Gilson HPLC (acidic condition), and the product fractions were combined and the solvent evaporated by GeneVac EZ-2 evaporator. Each compound was redissolved in MeOH/DCM (1/1) and an amine cartridge was used to neutralize the mixture to afford 8.4 mg (14%) of the title compound. 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. customevaporated
  9. customa GeneVac EZ-2 evaporator
  10. customthe mixture was placed in a Glas-Col evaporator overnight
  11. dissolutionThe resultant residue was then redissolved in MeOH/DMSO
  12. custompurified
  13. customthe solvent evaporated by GeneVac EZ-2 evaporator
  14. dissolutionEach compound was redissolved in MeOH/DCM (1/1)

Sources & evidence

ORD record
ord-fb3746b61d4c4b9387d92c4164d4918e
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

Loading…