2,6-Lutidine → HCID 67188740, compound

HRID 546104Notes

Reaction equation

HRID 546104 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.NC1C=CN(C[C:49]2[CH:50]=[C:51]([CH:55]=[CH:56][CH:57]=2)[C:52]([OH:54])=[O:53])N=1>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:49]3[CH:50]=[C:51]([CH:55]=[CH:56][CH:57]=3)[C:52]([OH:54])=[O:53])[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 19576665HCID 19576665, compoundHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

Product 1

HCID 67188740HCID 67188740, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 760 mg, 2.30 mmol) was dissolved in methylene chloride (10 mL) and a 2.0 M solution of oxalyl chloride in methylene chloride (1.15 mL, 2.30 mmol) was added and the reaction stirred at 25° C. for 15 min. The solution was chilled to 0° C. and 2,6-lutidine (0.536 mL, 4.6 mmol) was added dropwise. The reaction continued to stir at 0° C. for 15 min. The 3-(3-amino-pyrazol-1-ylmethyl)-benzoic acid (500 mg, 2.30 mmol) was added as a pre-dissolved reaction in methylene chloride (10 mL), the ice bath was removed and the reaction continued to stir at 25° C. for 25 min. The reaction was diluted with methylene chloride (100 mL), washed with water (2×30 mL), saturated aqueous brine solution (1×20 mL), dried over magnesium sulfate and concentrated in vacuo to a beige foam. Recrystallization from 17% ethyl acetate/methylene chloride afforded 3-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid (684 mg, 56%) as a white powder: ESI-LRMS m/e calcd for C26H28ClN3O5S [M+] 529.14, found 530.26 [M+H+].

Workup

  1. temperatureThe solution was chilled to 0° C.
  2. stirringto stir at 0° C. for 15 min
  3. customthe ice bath was removed
  4. stirringto stir at 25° C. for 25 min
  5. additionThe reaction was diluted with methylene chloride (100 mL)
  6. washwashed with water (2×30 mL), saturated aqueous brine solution (1×20 mL)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo to a beige foam
  9. customRecrystallization from 17% ethyl acetate/methylene chloride

Sources & evidence

ORD record
ord-1cbee0a4570c47d3b01374d733f92a6a
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

Loading…