Diisopropylethylamine → N-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-ylamino)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 418713ノート

反応式

HRID 418713 の反応式
[F:1][C:2]1[CH:7]=[C:6](N)[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH3:24])[CH:23]=3)[S:18][C:11]=12.[F:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]2([C:38]([OH:40])=O)[CH2:37][CH2:36]2)=[O:34])=[CH:28][CH:27]=1.CC[N:43](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([N:32]([C:29]2[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=2)[C:33]([C:35]2([C:38]([NH2:43])=[O:40])[CH2:36][CH2:37]2)=[O:34])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH3:24])[CH:23]=3)[S:18][C:11]=12

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 594577422-Fluoro-N1-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yl)benzene-1,4-diamine

生成物 1

HCID 66649155N-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-ylamino)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 58%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of 339 (80 mg, 0.24 mmol) and 1-(4-fluorophenylcarbamoyl) cyclopropanecarboxylic acid (181, 111 mg, 0.50 mmol) in anhydrous DMF were added DIPEA (123 μL, 0.71 mmol) and HATU reagent (256 mg, 0.67 mmol). The reaction mixture was stirred at room temperature overnight under nitrogen, diluted with AcOEt, and successively washed with sat. NaHCO3, water, sat. NH4Cl, water and brine, and concentrated. The crude material was first purified by flash column chromatography (eluents 2% of NH4OH in methanol/CH2Cl2: 10/90) and precipitated in AcOEt (with traces of acetone)/hexanes to afford title compound 336 (75 mg, 58% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.32 (s, 1H), 10.04 (s, 1H), 8.65 (bs, 1H), 8.18 (d, J=5.5 Hz, 1H), 7.78 (dd, J=12.9, 2.2 Hz, 1H), 7.77 (d, J=1.8 Hz, 1H), 7.68 (d, J=1.2 Hz, 1H), 7.68-7.60 (m, 2H), 7.50 (s, 1H), 7.44 (dd, J=8.4, 1.8 Hz, 1H), 7.30 (t, J=8.9 Hz, 1H), 7.15 (t, J=9.0 Hz, 2H), 6.36 (dd, J=5.5, 1.6 Hz, 1H), 3.70 (s, 3H), 1.47 (s, 4H). MS (m/z): 545.0 (M+H)+.

後処理

  1. washsuccessively washed with sat. NaHCO3, water, sat. NH4Cl, water and brine
  2. concentrationconcentrated
  3. customThe crude material was first purified by flash column chromatography (eluents 2% of NH4OH in methanol/CH2Cl2: 10/90)
  4. customprecipitated in AcOEt (with traces of acetone)/hexanes

出典と根拠

ORDレコード
ord-bc60f33518344cf69d4bd8c40b93afae
出典データセット
uspto-grants-2012_01
特許番号
US08093264B2

反応ノート

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