2,6-Lutidine → HCID 67191038, compound

HRID 546157Notes

Reaction equation

HRID 546157 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:26][CH:27]2CC[CH2:29][CH2:28]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21]CC(O)=O)[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[C:32](Cl)(=[O:36])[C:33](Cl)=O.NC1C=CN([CH2:44][C:45](C)([OH:47])[CH3:46])N=1.N1C(C)=CC=CC=1C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:26][CH:27]2[CH2:33][CH2:32][O:36][CH2:29][CH2:28]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:45]([OH:47])([CH3:46])[CH3:44])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 671905033-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid

Product 1

HCID 67191038HCID 67191038, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid (prepared as in PCT WO 2003/095438 A1, Example 20, 86 mg, 0.25 mmol) was dissolved in methylene chloride (3 mL) and N,N-dimethylfomamide (three drops) at 25° C. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 0.14 mL, 0.26 mmol) which produced gas evolution and it was then stirred at 25° C. for 30 minutes. After this time, the reaction was concentrated in vacuo and the residue was then taken up in methylene chloride (3 mL). This solution was then added dropwise to a flask containing a solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80, 39 mg, 0.25 mmol), 2,6-lutidine (58 μL, 0.49 mmol), and methylene chloride (2 mL) which was cooled to 0° C. The reaction was allowed to warm to 25° C. and stirred for a period of 2 h. After this time, the reaction quenched with a small amount of methanol and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 50% ethyl acetate/hexanes) to afford 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (69 mg, 57%) as a white foam.

Workup

  1. customat 25° C
  2. customproduced gas evolution and it
  3. concentrationAfter this time, the reaction was concentrated in vacuo
  4. additionThis solution was then added dropwise to a flask
  5. temperaturewas cooled to 0° C
  6. temperatureto warm to 25° C.
  7. stirringstirred for a period of 2 h
  8. customAfter this time, the reaction quenched with a small amount of methanol
  9. concentrationconcentrated with silica gel (2 g) in vacuo
  10. custompurified on Biotage Flash chromatography system (40S column, silica gel, 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-713bba9a744d4034b84c6a6f220b03d0
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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