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 2193784노트

반응식

HRID 2193784 반응식
[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

참가 물질

8

반응물 5

HCID 313Hydrochloric Acid2회HCID 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

생성물 1

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

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매2회HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-1eccea4b0d96494d9a674c210501b20e
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329726B2

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