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 2241381ノート

反応式

HRID 2241381 の反応式
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

参加物

3

反応物 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

生成物 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-carboxamide収率 30.3%

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1fe1dbcd775741a982f357e51a936254
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

反応ノート

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