2,6-Lutidine → HCID 67188972, compound

HRID 546268Notes

Reaction equation

HRID 546268 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:16]([CH2:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17]([OH:19])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:32][C:33]1[CH:37]=[CH:36][N:35]([CH2:38][C:39]([CH3:42])([OH:41])[CH3:40])[N:34]=1.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:16]([CH2:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17]([NH:32][C:33]2[CH:37]=[CH:36][N:35]([CH2:38][C:39]([OH:41])([CH3:40])[CH3:42])[N:34]=2)=[O:19])[CH:5]=[CH:6][C:7]=1[S:8]([CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1)(=[O:9])=[O:10]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 67191231HCID 67191231, compound

Product 1

HCID 67188972HCID 67188972, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent5×

Conditions

Temperature
25 °C

Procedure

A solution of (R)-2-(3-chloro-4-cyclopentanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (0.15 mmol) is dissolved in methylene chloride (5 mL) and N,N-dimethylformamide (one drop) and cooled to 0° C. To this solution is added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 1.2 equiv.) and it is then allowed to warm to 25° C. and stirred 1 h at 25° C. After this time, the reaction is concentrated in vacuo to ⅓ of the original volume. In a separate flask, a solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 1.5 equiv.), 2,6-lutidine (2.0 equiv.) and methylene chloride (5 mL) is cooled to 0° C. in an ice bath. To this solution is added the solution of the prepared acid chloride, diluted with another portion of methylene chloride (2 mL) dropwise. After the addition is complete the reaction is then allowed to warm to 25° C. and stirred for 16 hours. After this time the reaction mixture is diluted with methylene chloride (10 mL) transferred to a separatory funnel and washed with a saturated aqueous sodium bicarbonate solution (10 mL) and then a 1 N aqueous hydrochloric acid solution (10 mL) and then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (silica gel column) will afford (R)-2-(3-chloro-4-cyclopentanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide.

Workup

  1. concentrationAfter this time, the reaction is concentrated in vacuo
  2. additionAfter the addition
  3. temperatureto warm to 25° C.
  4. stirringstirred for 16 hours
  5. customtransferred to a separatory funnel
  6. washwashed with a saturated aqueous sodium bicarbonate solution (10 mL)
  7. dry with materiala 1 N aqueous hydrochloric acid solution (10 mL) and then dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification on an AnaLogix Intelliflash system (silica gel column)

Sources & evidence

ORD record
ord-814e2d82eed84e959c5a41411ffa700e
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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