2,6-Lutidine → HCID 24889329, compound

HRID 546177Notes

Reaction equation

HRID 546177 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:20][C:19](=[O:21])[CH2:18]2)[C:13](Cl)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[NH2:22][C:23]1[CH:27]=[CH:26][N:25]([CH2:28][C:29]([CH3:32])([OH:31])[CH3:30])[N:24]=1.N1C(C)=CC=CC=1C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:20][C:19](=[O:21])[CH2:18]2)[C:13]([NH:22][C:23]2[CH:27]=[CH:26][N:25]([CH2:28][C:29]([OH:31])([CH3:30])[CH3:32])[N:24]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 866180502(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclobutyl)-propionyl chloride

Product 1

HCID 24889329HCID 24889329, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclobutyl)-propionyl chloride in methylene chloride (0.036 M solution, 5 mL, 0.18 mmol) was slowly added to a cooled to 0° C. solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80, 31 mg, 0.20 mmol) and 2,6-lutidine (31 μl, 0.27 mmol) in methylene chloride (6 ml). The reaction continued to stir at 0° C. for 15 min and then at 25° C. for 4 h. After concentration in vacuo it was purified on an AnaLogix Intelliflash system (40 g column, 100% ethyl acetate) to afford 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(3-oxo-cyclobutyl)-propionamide (54 mg, 63%) as an off-white solid: [α]30589=−6.60° (c=5.9, CHCl3); 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03, 1.04 (2×s, 6H, 2×CH3), 1.93-2.40 (m, 3H, CH and CH2), 2.66-2.85 (m, 2H, 2×CH or 2×CH2), 2.98-3.12 (m, 2H, 2×CH or 2×CH2), 3.34 (s, 3H, SO2CH3), 3.87 (s, 2H, NCH2), 3.85-3.91 (m, 1H, ArCHCO2), 6.46 (d, J=2.3 Hz, 1H, Ar), 7.52 (d, J=2.3 Hz, 1H, Ar), 7.61 (dd, Jm=1.6 Hz, Jo=8.3 Hz, 1H, Ar), 7.73 (d, Jm=1.6 Hz, 1H, Ar), 8.02 (d, Jo=8.3 Hz, 1H, Ar), 10.84 (s, 1H, NH).

Workup

  1. waitat 25° C. for 4 h
  2. concentrationAfter concentration in vacuo it
  3. customwas purified on an AnaLogix Intelliflash system (40 g column, 100% ethyl acetate)

Sources & evidence

ORD record
ord-a4e61a3a1bb9473186cbdebbbd955f2d
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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