Hydrochloric Acid → N1-(4-(2-(6-(3-(Dimethylamino)propoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 2193784ノート

反応式

HRID 2193784 の反応式
[CH3:1][N:2]([CH3:31])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1.CCN(C(C)C)C(C)C.[CH3:41][O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[NH:49][C:50](=[O:55])[CH2:51][C:52](O)=[O:53].C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C.C(Cl)CCl>[CH3:31][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:52](=[O:53])[CH2:51][C:50]([NH:49][C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=4[O:42][CH3:41])=[O:55])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1

参加物

8

反応物 5

HCID 313Hydrochloric Acid2 回HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587900524-(2-(6-(3-(Dimethylamino)propoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorobenzenamine

生成物 1

HCID 58790091N1-(4-(2-(6-(3-(Dimethylamino)propoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide収率 33.6%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒2 回HCID 6228Dimethylformamide溶媒

実験手順

To a solution of aniline 380 (0.31 g, 0.71 mmol) and DIPEA (0.7 ml, 0.4 g, 3 mmol) in dry DMF (5 mL) was added acid 27 (0.30 g, 1.4 mmol), HOBt (0.040 g, 0.30 mmol), and EDC×HCl (0.40 g, 2.1 mmol) and the mixture was stirred at r.t. for 18 h. Additional EDC×HCl (0.050 g, 0.26 mmol) was added, and the mixture was stirred for a further 6 h. It was then partitioned between ethyl acetate and water. The organic phase was collected, washed with water, dried (anhydrous MgSO4), filtered, and concentrated. Flash chromatography (chloroform/NH4OH) of the residue followed by re-crystallization (90% ethyl acetate/methanol) provided 378 (0.15 g, 32% yield) as a colorless solid. 1H NMR (400 MHz. DMSO-d6) δ (ppm): 10.58 (br s, 1H); 9.63 (br s, 1H); 8.68 (dd, J=2.7, 0.8, 1H); 8.48 (d, J=5.5, 1H); 8.20 (dd, J=8.6, 2.7, 1H); 8.05 (d, J=7.6, 1H); 8.03 (s, 1H); 7.86 (dd, J=13.1, 2.3, 1H); 7.49 (t, J=8.8, 1H); 7.42 (dd, J=8.8, 1.4, 1H); 7.09-7.03 (m, 2H); 6.94 (dd, J=8.8, 0.7, 1H); 6.92-6.88 (m, 1H); 6.61 (dd, J=5.5, 1.0, 1H); 4.33 (t, J=6.7, 2H); 3.85 (s, 3H); 3.63 (s, 2H); 2.33 (t, J=7.2, 2H); 2.13 (s, 6H); 1.84 (quint, J=7.2, 2H). LRMS (M+H): 630.2.

後処理

  1. stirringthe mixture was stirred for a further 6 h
  2. customIt was then partitioned between ethyl acetate and water
  3. customThe organic phase was collected
  4. washwashed with water
  5. dry with materialdried (anhydrous MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customFlash chromatography (chloroform/NH4OH) of the residue followed by re-crystallization (90% ethyl acetate/methanol)

出典と根拠

ORDレコード
ord-1eccea4b0d96494d9a674c210501b20e
出典データセット
uspto-grants-2012_12
特許番号
US08329726B2

反応ノート

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