Hydrazine → N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide

HRID 1961171노트

반응식

HRID 1961171 반응식
[Cl:1][C:2]1[O:6][C:5]([C:7]([NH:9][C@@H:10]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH2:11][N:12]2C(=O)C3C(=CC=CC=3)C2=O)=[O:8])=[CH:4][C:3]=1[C:34]1[N:38]([CH3:39])[N:37]=[CH:36][C:35]=1[Cl:40].NN>O1CCCC1.CO>[NH2:12][CH2:11][C@@H:10]([NH:9][C:7]([C:5]1[O:6][C:2]([Cl:1])=[C:3]([C:34]2[N:38]([CH3:39])[N:37]=[CH:36][C:35]=2[Cl:40])[CH:4]=1)=[O:8])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31]

참가 물질

5

반응물 2

HCID 9321HydrazineHCID 578266885-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-furancarboxamide

생성물 1

HCID 57826499N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide수율 65%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-furancarboxamide (116 mg, 0.20 mmol) in tetrahydrofuran (1 ml) and methanol (1 ml) at 25° C. was added hydrazine (0.04 ml, 1.37 mmol) dropwise. After 12 h the solution was concentrated, dry loaded onto silica and purified by column chromatography (2% MeOH in DCM (1% NH4OH)). The free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (2 ml) to the residue in DCM (2 ml) affording the HCl salt of N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide (68 mg, 0.13 mmol, 65% yield) as a yellow solid: LCMS (ES) m/z=461, 463 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.80 (d, J=9.09 Hz, 1H) 8.03 (br. s., 3H) 7.66-7.73 (m, 2H) 7.58-7.61 (m, 1H) 7.52-7.59 (m, 2H) 7.40-7.48 (m, 1H) 4.5-4.57 (m, 1H) 3.77 (s, 3H) 2.98-3.09 (m, 4H).

후처리

  1. concentrationAfter 12 h the solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (2% MeOH in DCM (1% NH4OH))
  4. additionThe free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (2 ml) to the residue in DCM (2 ml)

출처 및 근거

ORD 기록
ord-922d0a362de94dc6901c90ece7921962
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410158B2

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