1-Hydroxybenzotriazole → N1-(4-(2-(3-((Dimethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 418653

반응식

HRID 418653 반응식
[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[O:20][C:21]3[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][C:22]=3[F:28])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)[CH3:3].[CH3:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH:37][C:38](=[O:43])[CH2:39][C:40](O)=[O:41].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O>[CH3:3][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[O:20][C:21]3[CH:27]=[CH:26][C:24]([NH:25][C:40](=[O:41])[CH2:39][C:38]([NH:37][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[O:30][CH3:29])=[O:43])=[CH:23][C:22]=3[F:28])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)[CH3:1]

참가 물질

6

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587901024-(2-(3-((Dimethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

생성물 1

HCID 16042361N1-(4-(2-(3-((Dimethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide수율 36.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of the amine 150 (334 mg, 0.85 mmol), 3-(2-methoxyphenylamino)-3-oxopropanoic acid (27) (355 mg, 1.70 mmol), 1-hydroxybenzotriazole (275 mg, 2.04 mmol) in dimethylformamide (8.5 mL) was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (391 mg, 2.04 mmol) and the reaction mixture was stirred at room temperature until completion of the reaction. The dimethylformamide was evaporated and the residue was quenched with a saturated solution of sodium bicarbonate. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous MgSO4, filtered and evaporated to afford title compound 146 as a white solid (180 mg, 36% yield). 1H NMR (DMSO-d6) 6 (Ppm): 10.59 (s, 1H), 9.64 (s, 1H), 8.52-8.50 (m, 1H), 8.08-8.06 (m, 2H), 7.88 (d, J=12.9 Hz, 1H), 7.78 (m, 2H), 7.51-7.38 (m, 4H), 7.07 (s, 2H), 6.92 (m, 1H), 6.65 (m, 1H), 3.86 (s, 3H), 3.65 (s, 2H), 3.48 (s, 2H), 2.18 (s, 6H). MS (m/z): 585.2 (M+H).

후처리

  1. customThe dimethylformamide was evaporated
  2. customthe residue was quenched with a saturated solution of sodium bicarbonate
  3. extractionThe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customevaporated

출처 및 근거

ORD 기록
ord-2640522338604c32b624ecd90d1bc515
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093264B2

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