2,6-Lutidine → (R)-N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide

HRID 546206Notes

Reaction equation

HRID 546206 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([O:21][CH3:22])[CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.[C:37]([Si:41]([CH3:52])([CH3:51])[O:42][CH2:43][CH2:44][N:45]1[CH:49]=[CH:48][C:47]([NH2:50])=[N:46]1)([CH3:40])([CH3:39])[CH3:38]>C(Cl)Cl.CN(C)C=O>[C:37]([Si:41]([CH3:52])([CH3:51])[O:42][CH2:43][CH2:44][N:45]1[CH:49]=[CH:48][C:47]([NH:50][C:8](=[O:9])[C@@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([O:21][CH3:22])[CH:12]=2)[CH2:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[N:46]1)([CH3:40])([CH3:39])[CH3:38]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 593449471-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-ylamineHCID 67191012(R)-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionic acid

Product 1

HCID 67193508(R)-N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamideYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

In a round bottom flask under argon was placed (R)-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionic acid (prepared in Example 100, 61 mg, 0.19 mmol) which was dissolved in methylene chloride (2 mL) and N,N-dimethylformamide (2 drops). To this solution was then added a solution of oxalyl chloride in methylene chloride (2.0 M solution, 100 μL, 0.20 mmol). Upon addition there was gas evolution. The reaction was stirred for 30 min at 25° C. After such time the reaction was cooled to 0° C. in an ice bath and 2,6-lutidine (47 μL, 0.38 mmol) and the reaction was stirred for 30 min at 0° C. To the solution was then added 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-ylamine (prepared in Example 67, 45 mg, 0.19 mmol). The reaction was then warmed to 25° C. and stirred for 2 h. After this time, the reaction was 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 (R)—N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide (15 mg, 15%).

Workup

  1. customIn a round bottom flask under argon was placed
  2. additionUpon addition there
  3. temperatureAfter such time the reaction was cooled to 0° C. in an ice bath
  4. temperatureThe reaction was then warmed to 25° C.
  5. stirringstirred for 2 h
  6. customAfter this time, the reaction was quenched with a small amount of methanol
  7. concentrationconcentrated with silica gel (2 g) in vacuo
  8. custompurified on Biotage Flash chromatography system (40S column, silica gel, 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-23f2b46c4db44627a23c65223cc2464d
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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