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 418713노트

반응식

HRID 418713 반응식
[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

참가 물질

7

반응물 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

생성물 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-dicarboxamide수율 58%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-bc60f33518344cf69d4bd8c40b93afae
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093264B2

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