Diisopropylethylamine → N-(4-(2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide

HRID 1475560노트

반응식

HRID 1475560 반응식
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:28]=[CH:27][C:25](N)=[CH:24][C:23]=3[F:29])[CH:13]=2)=[N:10][CH:11]=1.[C:30]1([NH:36][C:37]([C:39]2([C:42]([OH:44])=O)[CH2:41][CH2:40]2)=[O:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CC[N:47](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.C(OCC)(=O)C.CO>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:28]=[CH:27][C:25]([N:36]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:37]([C:39]4([C:42]([NH2:47])=[O:44])[CH2:40][CH2:41]4)=[O:38])=[CH:24][C:23]=3[F:29])[CH:13]=2)=[N:10][CH:11]=1

참가 물질

8

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 190968711-(Phenylcarbamoyl)cyclopropanecarboxylic acidHCID 579195224-((2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yl)oxy)-3-fluoroaniline

생성물 1

HCID 66599014N-(4-(2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide수율 35%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To intermediate 38 (0.46 g, 1.1 mmol) in dry DMF (20 mL) was added 1-(phenylcarbamoyl)cyclopropanecarboxylic acid (40) (0.46 g, 2.2 mmol) [US 2007/0004675 A1], DIPEA (0.98 mL, 5.6 mmol) and HATU (1.07 g, 2.81 mmol) and the mixture was stirred at r.t. for 18 h. The mixture was then partitioned between ethyl acetate and water; the organic phase was collected, washed with water, 1M NaOH, saturated NH4Cl, and brine, dried (anhydrous MgSO4), filtered and concentrated. Silica gel chromatography (2% methanol in ethyl acetate) afforded intermediate 41 (0.23 g, 34% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.37 (s, 1H), 9.98 (s, 1H), 8.68 (s, 1H), 8.53 (d, J=5.3 Hz, 1H), 8.40 (s, 1H), 8.31 (d, J=8.2 Hz, 1H), 7.97 (dd, J=8.2, 2.0 Hz, 1H), 7.90 (dd, J=13.1, 2.0 Hz, 1H), 7.62 (d, J=7.6 Hz, 2H), 7.53-7.46 (m, 2H), 7.30 (t, J=7.4 Hz, 2H), 7.06 (t, J=7.4 Hz, 1H), 6.66 (d, J=5.3 Hz, 1H), 5.88 (s, 1H), 4.11-3.97 (m, 4H), 1.47 (br s, 4H). MS (m/z): 597.2 (M+H).

후처리

  1. customThe mixture was then partitioned between ethyl acetate and water
  2. customthe organic phase was collected
  3. washwashed with water, 1M NaOH, saturated NH4Cl, and brine
  4. dry with materialdried (anhydrous MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-af44716426f74c908ad970b620f8b4bd
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018378B2

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