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 1401331ノート

反応式

HRID 1401331 の反応式
[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

参加物

8

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 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

生成物 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-dicarboxamide収率 35%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-0085094aa9ac4df3839d618bc4dc9a7f
出典データセット
uspto-grants-2014_12
特許番号
US08907091B2

反応ノート

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