Benzylamine → N-[1-(2-benzylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 546005Notes

Reaction equation

HRID 546005 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][CH2:22][C:23](O)=[O:24])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.[CH2:46]([NH2:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C(Cl)Cl>[CH2:46]([NH:53][C:23]([CH2:22][CH2:21][N:18]1[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[N:17]1)=[O:24])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 671905033-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid

Product 1

HCID 67188433N-[1-(2-benzylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution containing 3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid (prepared in example 9, 50 mg, 0.11 mmol) in methylene chloride (2 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (59 μL, 0.12 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (17 μL, 0.15 mmol) was added to the solution at 0° C. After 1 h, benzylamine (12 μL, 0.11 mmol) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford N-[1-(2-benzylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (19 mg, 32%) as a white solid: ESI-LRMS m/e calcd for C28H33ClN4O4S [M+] 556.2, found 557.4 [M+H+]; 1H NMR (400 MHz, CDCl3), δ ppm 1.04-1.22 (m, 2H, CH2), 1.42-1.93 (m, 8H, 4×CH2), 2.13-2.29 (m, 1H, CH), 2.67 (t, J=6.2 Hz, 2H, COCH2), 3.25 (s, 3H, SO2CH3), 3.52 (t, J=7.6 Hz, 1H, CH), 4.31 (t, J=6.2 Hz, 2H, NCH2), 4.36 (d, J=5.5 Hz, 2H, NCH2Ar), 5.91 (t, J=5.5 Hz, 1H, NH), 6.60 (d, J=2.3 Hz, 1H, Ar), 7.06-7.13 (m, 2H, Ar), 7.21-7.26 (m, 3H, Ar), 7.28 (d, J=2.3 Hz, 1H, Ar), 7.44 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.58 (d, Jm=1.7 Hz, 1 h, Ar), 8.67 (s, 1H, NH), 8.06 (d, Jo=8.2 Hz, 1H, Ar).

Workup

  1. waitAfter 1 h
  2. waitto proceed for 16 h
  3. washThe reaction solution was washed with 1.0 M aqueous hydrochloric acid solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride)

Sources & evidence

ORD record
ord-699fc0a39e2547ffa07d91f8680a8e1a
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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