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Trifluoroacetic acid → HCID 178480815、化合物

HRID 2241272
ノート
印刷プレビュー

反応式

HRID 2241272 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]([N:24]([C:33]5[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=5)[C:25]([C:27]5([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]5)=[O:26])=[CH:20][C:19]=4[F:40])=[C:11]3[C:10]([C:41]3[CH:45]=[C:44]([CH2:46][N:47]4[CH2:52][CH2:51][N:50]([CH3:53])[CH2:49][CH2:48]4)[O:43][CH:42]=3)=[N:9]2)=CC=1.COC1C=CC(CN2C3=NC=CC(OC4C=CC(N(C5C=CC(F)=CC=5)C(C5(C(N)=O)CC5)=O)=CC=4F)=C3C(C3OC(CN4CCN(C)CC4)=CC=3Br)=N2)=CC=1.C(O)(C(F)(F)F)=O>>[F:40][C:19]1[CH:20]=[C:21]([N:24]([C:33]2[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=2)[C:25]([C:27]2([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]2)=[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]([C:41]3[CH:45]=[C:44]([CH2:46][N:47]4[CH2:52][CH2:51][N:50]([CH3:53])[CH2:49][CH2:48]4)[O:43][CH:42]=3)[C:11]=12
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 3

HCID 6422Trifluoroacetic acidHCID 68512150N-(4-(1-(4-methoxybenzyl)-3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideHCID 68516486N-(4-(1-(4-methoxybenzyl)-3-(3-bromo-5-((4-methylpiperazin-1-yl)methyl)furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

生成物 1

HCID 178480815
HCID 178480815、化合物

実験手順

A 17:83 mixture of N-(4-(1-(4-methoxybenzyl)-3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide and N-(4-(1-(4-methoxybenzyl)-3-(3-bromo-5-((4-methylpiperazin-1-yl)methyl)furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide (26 mg, 0.035 mmol) were heated with TFA (0.5 mL) at 80° C. for 2 hours in a sealed vessel. After cooling to ambient temperature, the mixture was concentrated in vacuo, using toluene to azeotrope. The resulting solid was portioned between EtOAc (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc. The combined organic phases were washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated. The crude products were separated by preparative TLC (0.5 mm thickness; N-(4-(3-(3-bromo-5-((4-methylpiperazin-1-yl)methyl)furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide: Rf=0.33; N-(3-fluoro-4-(3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide: Rf=0.25), eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product, N-(3-fluoro-4-(3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, was obtained as a white powder (1 mg, 5%). HPLC: 98% purity (254 nm); LRMS (ESI+): 100% purity, 220 nm, 628 m/z (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 8.32 (d, J=5 Hz, 1H), 8.18 (m, 2H), 7.77 (m, 1H), 7.45 (m, 2H), 7.24 (m, 1H), 7.07 (t, J=9 Hz, 2H), 6.92 (s, 1H), 6.32 (d, J=5 Hz, 1H), 3.62 (s, 2H), 2.64 (br s, 8H), 2.37 (s, 3H), 1.83 (m, 2H), 1.63 (m, 2H).

後処理

  1. concentrationthe mixture was concentrated in vacuo
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc
  4. washThe combined organic phases were washed with brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude products were separated by preparative TLC (0.5 mm thickness; N-(4-(3-(3-bromo-5-((4-methylpiperazin-1-yl)methyl)furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide: Rf=0.33; N-(3-fluoro-4-(3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide: Rf=0.25)
  9. washeluting with 10% MeOH (containing 7N NH3) in CHCl3

出典と根拠

ORDレコード
ord-16ac8ff451804ce680a52540813162f7
出典データセット
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07723330B2

反応ノート

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