1-Hydroxybenzotriazole → (E)-N-methyl-N-(1-methylindol-5-ylmethyl)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide

HRID 1362247

반응식

HRID 1362247 반응식
[CH3:1][NH:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[CH:8]=[CH:7]2.Cl.Cl.[CH3:16][N:17]1[CH2:23][C:22]2[CH:24]=[C:25](/[CH:28]=[CH:29]/[C:30](O)=[O:31])[CH:26]=[N:27][C:21]=2[NH:20][C:19](=[O:33])[CH2:18]1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.C(OCC)C.O>[CH3:1][N:2]([CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[CH:8]=[CH:7]2)[C:30](=[O:31])/[CH:29]=[CH:28]/[C:25]1[CH:26]=[N:27][C:21]2[NH:20][C:19](=[O:33])[CH2:18][N:17]([CH3:16])[CH2:23][C:22]=2[CH:24]=1

참가 물질

9

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18525753n-Methyl-1-(1-methyl-1h-indol-5-yl)methanamineHCID 66967454(E)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid dihydrochloride

생성물 1

HCID 66966496(E)-N-methyl-N-(1-methylindol-5-ylmethyl)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide수율 78.3%

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of (methyl-(1-methyl-1H-indol-5-ylmethyl)amine (103 mg, 0.6 mmol), (E)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid dihydrochloride (160 mg, 0.5 mmol), HOBt (81 mg, 0.5 mmol) and diisopropylethylamine (0.41 mL, 2 mmol) in DMF (12 mL) was added EDC hydrochloride (114 mg, 0.6 mmol). The mixture was stirred overnight at room temperature. Water (75 mL) was added and the solution stirred for 1 hr. The precipitate was collected by filtration. The yellow solid was preabsorded onto silica gel and purified by column chromatography (95:5 CH2Cl2/MeOH) to give a yellow oil. Diethyl ether (100 mL) was added and the mixture was sonicated. The ether layer was decanted to afford (E)-N-methyl-N-(1-methylindol-5-ylmethyl)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide (158 mg, 78%) as a white solid and as a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6) δ 10.33 (d, J=4.3 Hz, 1H), 8.51 (d, J=6.1 Hz, 1H), 8.13 (s, 1H), 7.59-7.25 (m, 5H), 7.09-7.02 (m, 1H), 6.37 (s 1H), 4.67-4.86 (2×s, 2H), 3.72-3.79 (m, 5H), 3.42-3.38 (m, 2H), 3.06-2.87 (2×s, 3H), 2.37-2.33 (2×s, 3H); ESI MS m/z 404 [C23H25N5O2+H]+.

후처리

  1. stirringthe solution stirred for 1 hr
  2. filtrationThe precipitate was collected by filtration
  3. custompurified by column chromatography (95:5 CH2Cl2/MeOH)
  4. customto give a yellow oil
  5. customthe mixture was sonicated
  6. customThe ether layer was decanted

출처 및 근거

ORD 기록
ord-28f771492aa94dbe95540162aefbc970
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07879872B2

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