N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide → N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide

HRID 2241381노트

반응식

HRID 2241381 반응식
COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([CH:27]5[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([C:34]6[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=6)[C:28]5=[O:41])=[O:26])=[CH:20][C:19]=4[F:42])=[C:11]3[C:10]([NH:43][CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[N:9]2)=CC=1>C(O)(C(F)(F)F)=O>[F:42][C:19]1[CH:20]=[C:21]([NH:24][C:25]([CH:27]2[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([C:34]3[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=3)[C:28]2=[O:41])=[O:26])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:8][N:9]=[C:10]([NH:43][CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[C:11]=12

참가 물질

3

반응물 1

HCID 68512277N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide

생성물 1

HCID 59304319N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide수율 30.3%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

실험 절차

A solution of N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide (20 mg, 0.028 mmol) was heated in TFA (1 mL) at 55° C. for 3 hours. TFA was evaporated and EtOAc was added to dilute the mixture. The mixture washed with saturated aqueous NaHCO3, brine, dry with Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (20% MeOH in CH2Cl2) to afford the product (5 mg, 30% yield) as a white solid. LRMS (APCI pos) m/e 590.1 (M+1). 1H NMR (400 MHz, DMSO-d6): δ 12.15 (s, 1H), 10.20 (s, 1H), 8.10 (s, 1H), 7.82 (d, 1H), 7.18-7.50 (m, 7H), 5.98-6.00 (m, 1H), 5.10-5.20 (m, 1H), 3.90-4.02 (m, 2H), 3.40-3.62 (m, 2H), 2.62-2.80 (m, 1H), 2.15 (s, 3H), 1.90-2.02 (m, 5H), 1.50-1.88 (m, 6H).

후처리

  1. customTFA was evaporated
  2. additionEtOAc was added
  3. additionto dilute the mixture
  4. washThe mixture washed with saturated aqueous NaHCO3, brine
  5. dry with materialdry with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (20% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-1fe1dbcd775741a982f357e51a936254
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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