2,6-Lutidine → HCID 10027991, compound

HRID 719983Notes

Reaction equation

HRID 719983 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[O:28]1[CH2:32][CH2:31][CH2:30][CH:29]1[C:33]1[CH:34]=[CH:35][C:36]([NH2:39])=[N:37][CH:38]=1.NC1C=CC=CN=1.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:39][C:36]2[CH:35]=[CH:34][C:33]([CH:29]3[CH2:30][CH2:31][CH2:32][O:28]3)=[CH:38][N:37]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

10

Reactant 5

HCID 79372,6-LutidineHCID 104392-AminopyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 21897373HCID 21897373, compound

Product 1

HCID 10027991HCID 10027991, compoundYield 24%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 250 mg, 0.76 mmol) in methylene chloride (5 mL) was cooled to 0° C. and then was treated with a 2.0M solution of oxalyl chloride in methylene chloride (435 μL, 0.87 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min and then concentrated in vacuo. The resulting oil was dissolved in tetrahydrofuran (2 mL) at 25° C. and then was treated dropwise with a solution of the inseparable mixture of 5-(tetrahydro-furan-2-yl)-pyridin-2-ylamine and 2-aminopyridine (224 mg, 1.36 mmol) and 2,6-lutidine (263 μL, 2.27 mmol) in tetrahydrofuran (3 mL) via an addition funnel. The resulting cloudy solution was then stirred overnight for 16 h at 25° C. After this time, the reaction was diluted with water (10 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 65/35 to 50/50 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(tetrahydro-furan-2-yl)-pyridin-2-yl]-propionamide (86 mg, 24%) as a white foam: (ES)+-HRMS m/e calcd for C24H29ClN2O4S (M+H)+ 477.1610, found 477.1616.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resulting oil was dissolved in tetrahydrofuran (2 mL) at 25° C.
  3. stirringThe resulting cloudy solution was then stirred overnight for 16 h at 25° C
  4. extractionextracted with methylene chloride (3×25 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8b1b09aea7b740a7a3d6a8a8cdf78672
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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