1-Hydroxybenzotriazole → (E)-N-(benzofuran-5-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

HRID 1362409

반응식

HRID 1362409 반응식
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][NH:11][CH3:12])=[CH:9][C:4]=2[CH:3]=[CH:2]1.Cl.[O:14]=[C:15]1[NH:24][C:23]2[N:22]=[CH:21][C:20]([CH:25]=[CH:26][C:27]([OH:29])=O)=[CH:19][C:18]=2[CH2:17][CH2:16]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][N:11]([CH3:12])[C:27](=[O:29])/[CH:26]=[CH:25]/[C:20]3[CH:21]=[N:22][C:23]4[NH:24][C:15](=[O:14])[CH2:16][CH2:17][C:18]=4[CH:19]=3)=[CH:9][C:4]=2[CH:3]=[CH:2]1

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 218436191-(benzofuran-5-yl)-N-methylmethanamineHCID 66905306HCID 66905306, 화합물

생성물 1

HCID 16661127(E)-N-(benzofuran-5-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide수율 57.3%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
40 °C

실험 절차

To a solution of benzofuran-5-yl-N-methylmethanamine (297 mg, 1.84 mmol), 3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-acrylic acid hydrochloride (474 mg, 1.86 mmol), HOBt (252 mg, 1.86 mmol) and DIPEA (1.32 mL, 7.58 mmol) in anhydrous DMF (30 mL) was added EDC hydrochloride (357 mg, 1.86 mmol). The mixture was stirred overnight at 40° C. Water (70 mL) was added and the solution was stirred for 1 h. The reaction mixture was extracted with ethyl acetate (3×100 mL). Combined organic layers were washed with water (50 mL) and brine (50 mL) and concentrated to give a red solid which was purified by column chromatography (silica gel, 5% MeOH/CH2Cl2) to afford (E)-N-(benzofuran-5-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide (381 mg, 57%) as a red solid and a mixture of amide rotomers: 1H NMR (400 MHz, DMSO-d6) δ 10.64-10.62 (m, 1H), 8.36-8.33 (m, 1H), 8.07 (s, 1H), 7.97 (s, 1H), 7.59-7.49 (m, 3H), 7.38-7.17 (m, 2H), 6.94 (m, 1H), 4.89-4.69 (m, 2H), 3.10-2.85 (m, 5H), 2.54-2.52 (m, 2H); ESI MS m/z 362 [C21H19N3O3+H]+.

후처리

  1. stirringthe solution was stirred for 1 h
  2. extractionThe reaction mixture was extracted with ethyl acetate (3×100 mL)
  3. washCombined organic layers were washed with water (50 mL) and brine (50 mL)
  4. concentrationconcentrated
  5. customto give a red solid which
  6. customwas purified by column chromatography (silica gel, 5% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-7d1f43aef95d49cfbed7eb3529f799c7
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07879872B2

연결된 노트

불러오는 중…