Acetohydroxamic Acid → 1-(3-amino-1,2-benzisoxazol-5-yl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridine-7-one

HRID 1064038노트

반응식

HRID 1064038 반응식
C([NH:4][OH:5])(=O)C.C([O-])([O-])=O.[K+].[K+].F[C:13]1[CH:20]=[CH:19][C:18]([N:21]2[C:25]3[C:26](=[O:43])[N:27]([C:30]4[CH:35]=[CH:34][C:33]([N:36]5[CH2:41][CH2:40][CH2:39][CH2:38][C:37]5=[O:42])=[CH:32][CH:31]=4)[CH2:28][CH2:29][C:24]=3[C:23]([C:44]([F:47])([F:46])[F:45])=[N:22]2)=[CH:17][C:14]=1[C:15]#[N:16].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[NH2:16][C:15]1[C:14]2[CH:17]=[C:18]([N:21]3[C:25]4[C:26](=[O:43])[N:27]([C:30]5[CH:35]=[CH:34][C:33]([N:36]6[CH2:41][CH2:40][CH2:39][CH2:38][C:37]6=[O:42])=[CH:32][CH:31]=5)[CH2:28][CH2:29][C:24]=4[C:23]([C:44]([F:46])([F:45])[F:47])=[N:22]3)[CH:19]=[CH:20][C:13]=2[O:5][N:4]=1

참가 물질

7

반응물 4

HCID 1990Acetohydroxamic AcidHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 222500932-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile

생성물 1

HCID 101858661-(3-amino-1,2-benzisoxazol-5-yl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridine-7-one수율 81.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

실험 절차

Acetohydroxamic acid (54 mg, 0.72 mmol) and K2CO3 (0.2 g, 1.45 mmol) were added to 8 mL of DMF and 4 mL of H2O. The mixture was stirred at rt for 15 min, followed by addition of a solution of 2-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7,-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile (0.12 g, 0.24 mmol) in DMF(2 mL). The mixture was stirred at rt overnight. The mixture was then partitioned between ethylacetate (40 mL) and water (20 mL), washed with H2O (20 mL×3) and brine (20 mL), dried over Na2SO4, filtered, and concentrated. HPLC (C18 RP., 0.5% TFA, H2O/MeCN gradient) purification gave 100 mg (67% yield) of the title compound as its TFA salt. LRMS (ESI−): 623.4 (M+TFA−H)−. 1H NMR (CDCl3) δ 7.80 (s, 1H), 7.72 (d, 1H), 7.44 (d, 1H), 7.34-7.24 (m, 4H), 4.16 (t, 2H), 3.98 (br, 2H), 3.61 (br, 2H), 3.20 (t, 2H), 2.60 (br, 2H), 1.98-1.89 (m, 4H).

후처리

  1. stirringThe mixture was stirred at rt overnight
  2. customThe mixture was then partitioned between ethylacetate (40 mL) and water (20 mL)
  3. washwashed with H2O (20 mL×3) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customHPLC (C18 RP., 0.5% TFA, H2O/MeCN gradient) purification

출처 및 근거

ORD 기록
ord-85d2f5e1a2894942a85dcc1d97540b06
출처 데이터셋
uspto-grants-2005_11
특허 번호
US06967208B2

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