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

HRID 546004Notes

Reaction equation

HRID 546004 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.[N:38]1[C:43](C)=[CH:42][CH:41]=[CH:40][C:39]=1[CH3:45].NC1C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:26][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][CH2:22][C:23](=[O:24])[NH:38][C:43]3[CH:45]=[CH:39][CH:40]=[CH:41][CH:42]=3)[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

6

Reactant 4

HCID 6115AnilineHCID 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 671891802(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-phenylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-propionamide

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, 100 mg, 0.21 mmol) in methylene chloride (2 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (118 μL, 0.24 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (28 μL, 0.24 mmol) was added to the solution at 0° C. After 1 h, aniline (21 μL, 0.21 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 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-phenylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-propionamide was obtained (71 mg, 61%) as a white solid: ESI-LRMS m/e calcd for C27H31ClN4O4S [M+] 542.2, found 543.3 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.01-1.20 (m, 2H, CH2), 1.40-1.88 (m, 8H, 4×CH2), 2.11-2.26 (m, 1H, CH), 2.66-2.76 (m, 2H, COCH2), 3.25 (s, 3H, SO2CH3), 3.64 (t, J=7.5 Hz, 1H, CH), 4.22-4.30 (m, 2H, NCH2), 6.53 (d, J=2.2 Hz, 1H, Ar), 7.05 (t, J=7.4 Hz, 1H, Ar), 7.18-7.25 (m, 3H, Ar), 7.37 (d, Jo=7.8 Hz, 2H, Ar), 7.43 (dd, Jo=8.3, Jm=1.6 Hz. 1H, Ar), 7.58 (d, Jm=1.6 Hz, 1H, Ar), 7.88 (s, 1H, NH), 8.01 (d, Jo=8.3 Hz, 1H, Ar), 8.62 (s, 1H, NH).

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-d7b955560d84480ca4d0882f88226fcb
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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