Oxalyl chloride → HCID 67190211, compound

HRID 546248Notes

Reaction equation

HRID 546248 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([S:17]([CH3:20])(=[O:19])=[O:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C.[NH2:36][C:37]1[CH:41]=[CH:40][N:39]([CH2:42][C:43]([CH3:46])([OH:45])[CH3:44])[N:38]=1>C1C=CC=CC=1.CN(C=O)C.C(Cl)Cl>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([S:17]([CH3:20])(=[O:19])=[O:18])[CH:12]=2)[C:8]([NH:36][C:37]2[CH:41]=[CH:40][N:39]([CH2:42][C:43]([OH:45])([CH3:44])[CH3:46])[N:38]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 67190471HCID 67190471, compound

Product 1

HCID 67190211HCID 67190211, compoundYield 32.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of (R)-3-cyclopentyl-2-(3-methylsulfonyl-phenyl)-propionic acid (200 mg, 0.65 mmol) in benzene (10 mL) was added oxalyl chloride (123 mg, 0.97 mmol) and DMF (1 drop) and the reaction was stirred at 25° C. for 1 h. The reaction was concentrated under reduced pressure and the residue was dissolved into methylene chloride (10 mL) under a nitrogen atmosphere. To this stirred solution was added N,N′-diisopropylethylamine (125 mg, 0.97 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 130 mg, 0.84 mmol). The reaction was stirred at 25° C. for 18 h and then diluted with methylene chloride (30 mL). The methylene chloride was washed with water, 2 N aqueous hydrochloric acid solution, saturated sodium bicarbonate and saturated sodium chloride solution and then dried over magnesium sulfate. Filtration and concentration afforded the crude product which was purified by flash column chromatography (Biotage 40S Flash Column; 80% ethyl acetate/hexanes) to yield (R)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(3-methanesulfonyl-phenyl)-propionamide (92 mg, 32%) as a white solid: [α]28589=−8.9° (c=0.1, methanol); ES-HRMS m/e calcd for C22H31N3O4S (M+H)+ 434.2108, observed 434.2108; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.05 (s, 3H, CH3), 1.12 (m, 2H, CH2), 1.37-1.79 (m, 8H, 4×CH2), 2.13 m, 1H, CH), 3.21 (s, 3H, SO2CH3), 3.86 (s, 2H, NCH2), 3.93 (m, 1H, ArCHCO), 4.64 (s, 1H, OH), 6.46 (d, J=2.2 Hz, 1H, Ar), 7.50 (d, J=2.2 Hz, 1H, Ar), 7.61 (t, J=7.7 Hz, 1H, Ar), 7.73 (d, J=7.7 Hz, 1H, Ar), 7.82 (d, J=7.7 Hz, 1H, Ar), 7.93 (s, 1H, Ar), 10.78 (s, 1H, NH).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved into methylene chloride (10 mL) under a nitrogen atmosphere
  3. stirringThe reaction was stirred at 25° C. for 18 h
  4. washThe methylene chloride was washed with water, 2 N aqueous hydrochloric acid solution, saturated sodium bicarbonate and saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltration and concentration
  7. customafforded the crude product which
  8. customwas purified by flash column chromatography (Biotage 40S Flash Column; 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ad21c3a64c9c45418b6d9af7b5937475
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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