4-Methylmorpholine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-propionyl-1H-pyrazol-3-yl)-propionamide

HRID 546041

Reaction equation

HRID 546041 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][NH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].CN1CCOCC1.[C:34](Cl)(=[O:37])[CH2:35][CH3:36]>C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:21][CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([C:34](=[O:37])[CH2:35][CH3:36])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 62324Propionyl chlorideHCID 178504752HCID 178504752, compound

Product 1

HCID 671922152(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-propionyl-1H-pyrazol-3-yl)-propionamideYield 43.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

2(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1H-pyrazol-3-yl)-propionamide (prepared in example 2, 100 mg, 0.25 mmol) was dissolved in methylene chloride (2 mL). N-Methyl-morpholine (31 μL, 0.28 mmol) was added followed by propionyl chloride (26 μL, 0.28 mmol). The reaction stirred at 25° C. for 2.5 h. The solution was diluted with ethyl acetate (25 mL), washed with water (2×15 mL), saturated aqueous saturated aqueous brine solution (2×15 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-propionyl-1H-pyrazol-3-yl)-propionamide (49 mg, 43%) as a white powder: ESI-LRMS m/e calcd for C21H26ClN3O4S [M+] 451.1, found 452.2 [M+H+], 396.0 [M−COCH2CH3+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.08-1.24 (m, 2H, CH2), 1.27 (t, J=7.3 Hz, 1H, CH3), 1.44-1.97 (m, 8H, 4×CH2), 2.14-2.32 (m, 1H, CH), 2.99 (q, J=7.3 Hz, 2H, CH2), 3.27 (s, 3H, SO2CH3), 3.57 (t, J=7.5 Hz, 1H, CH), 6.98 (d, J=2.1, 1H, Ar), 7.46 (dd, Jo=8.1, Jm=1.5 Hz. 1H, Ar), 7.59 (d, Jm=1.5 Hz, 1 H, Ar), 7.81 (s, 1H, NH), 8.10-8.15 (m, 2H, Ar).

Workup

  1. washwashed with water (2×15 mL), saturated aqueous saturated aqueous brine solution (2×15 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a6ccce5e278642709346e983a02f31f7
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Linked notes

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