Oxalyl chloride → HCID 67188571, compound

HRID 546249Notes

Reaction equation

HRID 546249 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.[CH3:36][O:37][C:38]([CH3:47])([CH3:46])[CH2:39][N:40]1[CH:44]=[CH:43][C:42]([NH2:45])=[N:41]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:45][C:42]2[CH:43]=[CH:44][N:40]([CH2:39][C:38]([O:37][CH3:36])([CH3:46])[CH3:47])[N:41]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 668999341-(2-methoxy-2-methylpropyl)-1H-pyrazol-3-amineHCID 67190471HCID 67190471, compound

Product 1

HCID 67188571HCID 67188571, compoundYield 55%

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 (prepared in Example 134, 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 3 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-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-ylamine (prepared in Example 94, 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; 70% ethyl acetate/hexanes) to yield (R)-3-cyclopentyl-2-(3-methanesulfonyl-phenyl)-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (157 mg, 55%) as a white solid: ES-HRMS m/e calcd for C23H33N3O4S (M+H)+ 448.2265, observed 448.2265; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (s, 3H, CH3), 1.05 (s, 3H, CH3), 1.10 (m, 2H, CH2), 1.35-1.80 (m, 8H, 4×CH2), 2.13 (m, 1H, CH), 3.13 (s, 3H, OCH3), 3.21 (s, 3H, SO2CH3), 3.94 (m, 1H, ArCHCO), 3.96 (s, 2H, NCH2), 6.46 (d, J=2.1 Hz, 1H, Ar), 7.47 (d, J=2.1 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), 7.94 (s, 1H, Ar), 10.79 (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; 70% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e0c401f15ed34911b97e9960d89666a9
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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