1-Hydroxybenzotriazole → HCID 86710223, compound

HRID 2405904Notes

Reaction equation

HRID 2405904 reaction equation
[CH3:1][C:2]([S:22]([CH3:25])(=[O:24])=[O:23])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([B:13]2[O:17][C:16]([CH3:19])([CH3:18])[C:15]([CH3:21])([CH3:20])[O:14]2)[CH:10]=[N:9]1)[C:3](O)=[O:4].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[O:48]1[CH2:53][CH2:52][CH2:51][CH2:50][CH:49]1[O:54][NH2:55]>CS(C)=O.CCOC(C)=O.O>[CH3:1][C:2]([S:22]([CH3:25])(=[O:24])=[O:23])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([B:13]2[O:17][C:16]([CH3:18])([CH3:19])[C:15]([CH3:20])([CH3:21])[O:14]2)[CH:10]=[N:9]1)[C:3]([NH:55][O:54][CH:49]1[CH2:50][CH2:51][CH2:52][CH2:53][O:48]1)=[O:4]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817773HCID 70817773, compound

Product 1

HCID 86710223HCID 86710223, compoundYield 52.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2-methyl-2-(methylsulfonyl)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]butanoic acid (7.0 g, 0.019 mol) in DMSO (300 mL) was added HOBT (3.24 g, 0.024 mol). The reaction solution was stirred at room temperature for 20 min, EDCI.HCl (4.6 g, 0.024 mol) and O-tetrahydro-2H-pyran-2-yl-hydroxylamine (2.5 g, 0.021 mol) were added at room temperature and the reaction mixture was stirred at room temperature overnight. Water (200 mL) and EtOAc (200 mL) were added and the layers were separated. The aqueous layer was extracted with EtOAc (100 mL×3). The organic layers were combined and washed with H2O (50 mL), brine (20 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography on silica gel eluting with MeOH/DCM (0-10% gradient) to give a 2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]butanamide (4.7 g, 52%). LC-MS M+H+472.2.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (100 mL×3)
  4. washwashed with H2O (50 mL), brine (20 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel eluting with MeOH/DCM (0-10% gradient)

Sources & evidence

ORD record
ord-fb682cd499c649fc83aeb8ece87241b4
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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