1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 67326745, compound

HRID 1500747Notes

Reaction equation

HRID 1500747 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[OH:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]2[CH:23]=[N:24][N:25]3[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=23)[N:17]=1.F[P-](F)(F)(F)(F)F.[N:40]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[N:41]1.N12CCCN=C1CCCCC2>CN(C=O)C>[C:31]([C:28]1[CH:29]=[CH:30][N:25]2[N:24]=[CH:23][C:22]([C:18]3[N:17]=[C:16]([NH:1][C@@H:2]4[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]4)[CH:21]=[CH:20][N:19]=3)=[C:26]2[CH:27]=1)#[N:32].[N:40]1([O:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([C:22]3[CH:23]=[N:24][N:25]4[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=34)[N:17]=2)[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[N:41]1

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 178510194HCID 178510194, compound

Product 2

HCID 67326745HCID 67326745, compoundYield 66%HCID 67326806HCID 67326806, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Tert-butyl (3R)-3-aminopiperidine-1-carboxylate (1.49 g, 7.46 mmol) was added to a stirred solution of 3-(4-hydroxypyrimidin-2-yl)pyrazolo[1,5-a]pyridine-5-carbonitrile (Preparation 3b, 0.70 g, 2.98 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (1.71 g, 3.88 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.67 mL g, 4.48 mmol) in N,N′-dimethylformamide (15 mL) and the resulting mixture was stirred at room temperature for 16 hours. Then the solvent was removed under reduced pressure and the residue was taken up in a mixture of dichloromethane and 4% aqueous sodium hydrogencarbonate solution. The organic layer was separated, dried (MgSO4) and evaporated in vacuo. The crude product was purified by flash chromatography (99:1 dichloromethane/methanol) to give a residue that was repurified by reverse phase chromatography (C-18 silica from Waters, water/acetonitrile/methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to give the title compound (0.83 g, 66%) and 3-(4-(1H-benzo[d][1,2,3]triazol-1-yloxy) pyrimidin-2-yl)pyrazolo[1,5-a]pyridine-5-carbonitrile (0.10 g) as the main reaction byproduct.

Workup

  1. customThen the solvent was removed under reduced pressure
  2. additionthe residue was taken up in a mixture of dichloromethane and 4% aqueous sodium hydrogencarbonate solution
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe crude product was purified by flash chromatography (99:1 dichloromethane/methanol)
  7. customto give a residue that
  8. customwas repurified by reverse phase chromatography (C-18 silica from Waters, water/acetonitrile/methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-2276962083be43888a8b4137742d9da7
Source dataset
uspto-grants-2015_12
Patent number
US09206183B2

Reaction notes

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