Diisopropylethylamine → 1-[1-(4-chlorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propan-1-one

HRID 710680노트

반응식

HRID 710680 반응식
[CH3:1][C:2]1[N:6]([CH:7]([CH3:11])[C:8]([OH:10])=O)[N:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][NH:27][C:26]=3[CH:25]=[N:24]2)=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][N:27]([C:8](=[O:10])[CH:7]([N:6]4[C:2]([CH3:1])=[N:3][C:4]([C:12]([F:15])([F:14])[F:13])=[N:5]4)[CH3:11])[C:26]=3[CH:25]=[N:24]2)=[CH:21][CH:22]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 680410521-(4-chlorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridineHCID 867116872-[5-Methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid

생성물 1

HCID 733362111-[1-(4-chlorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propan-1-one수율 30%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid (0.048 g, 0.21 mmol) and 1-(4-chlorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine (0.050 g, 0.21 mmol) in DMF (1 mL) were added Hunig's base (0.055 g, 0.42 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophosphate methanaminium (HATU) (0.090 g, 0.23 mmol). The mixture was stirred at room temperature for 1 hour, and then partitioned between water (4 mL) and ethyl acetate (6 mL). The organic layer was washed with brine, dried (Na2SO4), filtered, concentrated in vacuo, and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the desired product as a white solid (0.028 g, 0.063 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.43 (s, 4H), 5.60 (q, J=7.1 Hz, 1H), 3.77 (ddd, J=12.6, 7.5, 3.0 Hz, 1H), 3.52 (ddd, J=12.3, 8.3, 3.0 Hz, 1H), 2.84 (tt, J=6.9, 3.3 Hz, 2H), 2.52 (s, 3H), 2.09-1.81 (m, 5H); MS: (ES) m/z calculated for C19H18ClF3N6O [M+H]+ 439.1, found 438.9.

후처리

  1. custompartitioned between water (4 mL) and ethyl acetate (6 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

출처 및 근거

ORD 기록
ord-7cb17d4e5dd148fd97cf985ac5712e10
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181241B2

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