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Trifluoroacetic acid → 1-(3-(Dimethylphosphoryl)phenyl)-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

HRID 409959
ノート
印刷プレビュー

反応式

HRID 409959 の反応式
C(OC(=O)[N:7]([CH2:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH:38][C:39]4[CH:44]=[CH:43][CH:42]=[C:41]([P:45]([CH3:48])([CH3:47])=[O:46])[CH:40]=4)=[O:37])=[CH:31][C:30]=3[F:49])[CH:20]=2)=[CH:17][CH:18]=1)[CH2:8][CH2:9][O:10][CH3:11])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:48][P:45]([C:41]1[CH:40]=[C:39]([NH:38][C:36]([NH:35][C:32]2[CH:33]=[CH:34][C:29]([O:28][C:25]3[CH:24]=[CH:23][N:22]=[C:21]4[CH:20]=[C:19]([C:16]5[CH:17]=[CH:18][C:13]([CH2:12][NH:7][CH2:8][CH2:9][O:10][CH3:11])=[CH:14][N:15]=5)[S:27][C:26]=34)=[C:30]([F:49])[CH:31]=2)=[O:37])[CH:44]=[CH:43][CH:42]=1)([CH3:47])=[O:46]
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 2

HCID 6422Trifluoroacetic acidHCID 67049417Tert-butyl(6-(7-(4-(3-(3-(dimethylphosphoryl)phenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate

生成物 1

HCID 670482601-(3-(Dimethylphosphoryl)phenyl)-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea収率 38.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane
溶媒

実験手順

To a solution of compound 288 (230 mg, 0.32 mmol) in dichloromethane (7 mL) under nitrogen at room temperature was added trifluoroacetic acid (2.5 mL, 32 mmol). The reaction mixture was stirred for 16 h at room temperature. The solvent was removed under reduced pressure and a saturated aqueous solution of sodium bicarbonate was added. The aqueous phase was extracted with ethyl acetate (3×), the combined organic layers were concentrated. The residue was purified via Biotage (linear gradient 0-20%, methanol/dichloromethane; 25M column) to afford compound 289 as an off-white solid (75.3 mg, 0.122 mmol, 38.0%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.15 (s, 1H), 9.06 (s, 1H), 8.57 (d, J=1.6 Hz, 1H), 8.53 (d, J=5.6 Hz, 1H), 8.31 (s, 1H), 8.23 (d, J=8.0 Hz, 1H), 7.92-7.83 (m, 2H), 7.76 (dd, J=13.2, 2.4 Hz, 1H), 7.67-7.62 (m, 1H), 7.49-7.42 (m, 2H), 7.41-7.33 (m, 1H), 7.32-7.26 (m, 1H), 6.67 (d, J=5.6 Hz, 1H), 3.78 (s, 2H), 3.54-3.34 (2H, hidden under water signal), 3.24 (s, 3H), 2.65 (t, J=5.6 Hz, 2H), 1.65 (d, J=13.2 Hz, 6H). MS (m/z): 620.4 (M+H).

後処理

  1. customThe solvent was removed under reduced pressure
  2. additiona saturated aqueous solution of sodium bicarbonate was added
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. concentrationthe combined organic layers were concentrated
  5. customThe residue was purified via Biotage (linear gradient 0-20%, methanol/dichloromethane; 25M column)

出典と根拠

ORDレコード
ord-60676b84c26e497895503bcdf9812077
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08759522B2

反応ノート

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