4-Methylmorpholine → 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-propionylamino-benzyl)-1H-pyrazol-3-yl]-propionamide

HRID 546098Notes

Reaction equation

HRID 546098 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][CH:34]=1)[CH2:5][N:6]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:31])[C@@H:13]([C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[C:22]([Cl:30])[CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[N:7]1.CN1CCOCC1.[C:42](Cl)(=[O:45])[CH2:43][CH3:44]>C(Cl)Cl>[Cl:30][C:22]1[CH:21]=[C:20]([C@@H:13]([CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:12]([NH:11][C:8]2[CH:9]=[CH:10][N:6]([CH2:5][C:4]3[CH:32]=[CH:33][CH:34]=[C:2]([NH:1][C:42](=[O:45])[CH2:43][CH3:44])[CH:3]=3)[N:7]=2)=[O:31])[CH:25]=[CH:24][C:23]=1[S:26]([CH3:29])(=[O:28])=[O:27]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62324Propionyl chlorideHCID 67190250N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 671888522-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-propionylamino-benzyl)-1H-pyrazol-3-yl]-propionamideYield 61.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

N-[1-(3-Amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide prepared in example 58 (110 mg, 0.22 mmol) was dissolved in methylene chloride (2 mL) and N-methyl-morpholine (26 μL, 0.24 mmol) was added. Propionyl chloride (19 μL, 0.22 mmol) was added and the reaction stirred at 25° C. for 30 min. The reaction was concentrated in vacuo to give a beige foam. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 20% ethyl acetate/methylene chloride) afforded 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-propionylamino-benzyl)-1H-pyrazol-3-yl]-propionamide (75 mg, 61%) as a white powder: ESI-LRMS m/e calcd for C28H33ClN4O4S [M+] 556.19, found 557.27 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.07-1.19 (m, 2H, CH2), 1.23 (t, J=7.5 Hz, 3H, CH3), 1.41-1.92 (m, 8H, 4×CH2), 2.15-2.27 (m, 1H, CH), 2.36 (m, 2H, NCOCH2), 3.25 (s, 3H, SO2CH3), 3.56 (t, J=7.75 Hz, 1 H, CH), 5.09 (s, 2H, NCH2), 6.68 (d, J=2.0 Hz, 1H, Ar), 6.86 (d, Jo=7.8 Hz, 1H, Ar), 7.18-7.23 (m, 1H, Ar), 7.24 (s, 1H, NH), 7.30 (d, J=2.0 Hz, 1H, Ar), 7.33-7.42 (m, 2H, Ar), 7.44 (d, Jo=8.2 Hz. 1H, Ar), 7.58 (s, 1H, Ar), 8.04 (d, Jo=8.2 Hz. 1H, Ar), 8.05 (brs, 1H, NH).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customto give a beige foam
  3. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 20% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-61bce645554c4bda99d06c6810f71048
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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