Dimethylformamide → HCID 178504752, 화합물

HRID 545985

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HRID 545985 반응식
[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]

참가 물질

8

반응물 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, 화합물

생성물 1

HCID 178504752HCID 178504752, 화합물수율 43.8%

시약·촉매·용매 1

HCID 6212Chloroform용매

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온도
25 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-78513bbbcb0c4be9974be3d1db9ccd3c
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935699B2

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