Dimethylformamide → HCID 178504752, compound

HRID 545985

Reaction equation

HRID 545985 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](C)[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.C(Cl)Cl.CN(C)C=O.N1C=CC(N)=N1.N1C(C)=CC=CC=1C>C(Cl)(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][NH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazoleHCID 178418806HCID 178418806, compound

Product 1

HCID 178504752HCID 178504752, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
25 °C

Procedure

The 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) was dissolved in chloroform (1 mL). To this solution was added a 2.0 M solution of oxalylchloride in methylene chloride (151 μL, 0.30 mmol) and N,N-dimethylformamide (23 μL, 0.30 mmol). The solution was allowed to stir for 1 h at 25° C., after which 1H-pyrazol-3-ylamine (25 mg, 0.30 mmol) was added along with 2,6-lutidine (70 μL, 0.60 mmol). The reaction was allowed to proceed for 40 h. The solvent was removed in vacuo and the crude material was purified by reverse phase preparative HPLC (Column: Thomson C18 ODSA, 5 micron, 50×21.2 mm ID; 30% acetonitrile/water to 100% acetonitrile/water; 30 mL/min flow rate for 15 min run) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1H-pyrazol-3-yl)-propionamide (52 mg, 43%) as a white solid: ESI-LRMS m/e calcd for C18H22ClN3O3S [M+] 395.1, found 396.1 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.00-1.19 (m, 2H, CH2), 1.34-1.91 (m, 8H, 4×CH2), 2.08-2.29 (m, 1H, CH), 3.24 (s, 3H, SO2CH3), 3.65 (t, J=7.6 Hz, 1H, CH), 6.54 (d, 1H, J=1.7, Ar), 7.39 (m, 2H, Ar), 7.54 (d, Jm=1.3 Hz, 1H, Ar), 7.94 (d, Jo=8.2 Hz, 1H, Ar), 9.26 (s, 1H, NH).

Workup

  1. waitto proceed for 40 h
  2. customThe solvent was removed in vacuo
  3. customthe crude material was purified by reverse phase preparative HPLC (Column: Thomson C18 ODSA, 5 micron, 50×21.2 mm ID; 30% acetonitrile/water to 100% acetonitrile/water; 30 mL/min flow rate for 15 min run)

Sources & evidence

ORD record
ord-78513bbbcb0c4be9974be3d1db9ccd3c
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Linked notes

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