2,6-Lutidine → HCID 67188862, compound

HRID 546037Notes

Reaction equation

HRID 546037 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[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.[Cl:42][C:43]1[CH:44]=[C:45]([CH:53]=[CH:54][C:55]=1[Cl:56])CN1C=CC(N)=N1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:53]3[CH:45]=[CH:44][C:43]([Cl:42])=[C:55]([Cl:56])[CH:54]=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 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 7019302HCID 7019302, compoundHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

Product 1

HCID 67188862HCID 67188862, compoundYield 79.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (181 μL, 0.36 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (70 μL, 0.61 mmol) was added to the solution at 0° C. After 1 h, the crude 1-(3,4-dichloro-benzyl)-1H-pyrazol-3-ylamine (0.42 mmol based on theory) 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-(3,4-dichloro-benzyl)-1H-pyrazol-3-yl]-propionamide (133 mg, 79%) as a white solid: ESI-LRMS m/e calcd for C25H26Cl3N3O3S [M+] 553.1, found 554.2 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.22 (m, 2H, CH2), 1.42-1.90 (m, 8H, 4×CH2), 2.09-2.28 (m, 1H, CH), 3.24 (s, 3 H, SO2CH3), 3.57 (t, J=7.6 Hz, 1H, CH), 5.07 (s, 2H, NCH2), 6.71 (d, J=2.3 Hz, 1H, Ar), 6.95 (dd, Jo=8.2, Jm=2.0 Hz, 1H, Ar), 7.21 (d, Jm=2.0 Hz, 1H, Ar), 7.31 (d, J=2.3 Hz, 1H, Ar), 7.36 (d, Jo=8.2 Hz, 1H, Ar), 7.44 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.58 (d, Jm=1.7 Hz, 1H, Ar), 8.05 (d, Jo=8.2 Hz, 1H, Ar), 8.14 (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-02b4fde84665438b9ad5d1b2babec6d3
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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