Methyl iodide → N-[3-(4-hydroxy-1-isopentyl-2-oxo-5,6,7,8,9,9a-hexahydro-4aH-cyclohepta[b]pyridin-3-yl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]-N-methyl-methanesulfonamide

HRID 731332노트

반응식

HRID 731332 반응식
[C:1](=O)([O-])[O-].[K+].[K+].IC.[OH:9][C:10]1[CH:11]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH:12]2[N:13]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:14](=[O:33])[C:15]=1[C:16]1[NH:21][C:20]2[CH:22]=[CH:23][C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][C:19]=2[S:18](=[O:32])(=[O:31])[N:17]=1>CN(C)C=O>[OH:9][C:10]1[CH:11]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH:12]2[N:13]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:14](=[O:33])[C:15]=1[C:16]1[NH:21][C:20]2[CH:22]=[CH:23][C:24]([N:26]([CH3:1])[S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][C:19]=2[S:18](=[O:31])(=[O:32])[N:17]=1

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 135955693N-[3-(4-hydroxy-1-isopentyl-2-oxo-5,6,7,8,9,9a-hexahydro-4aH-cyclohepta[b]pyridin-3-yl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

생성물 1

HCID 135955694N-[3-(4-hydroxy-1-isopentyl-2-oxo-5,6,7,8,9,9a-hexahydro-4aH-cyclohepta[b]pyridin-3-yl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]-N-methyl-methanesulfonamide수율 34.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
25 °C

실험 절차

Potassium carbonate (0.067 g, 0.488 mmol) and iodomethane (0.017 mL, 0.268 mmol) were added sequentially to a solution of N-{3-[4-hydroxy-1-(3-methyl-butyl)-2-oxo-2,4a,5,6,7,8,9,9a-octahydro-1H-cyclohepta[b]pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (prepared as described in Example 33b, 0.128 g, 0.244 mmol) in N,N-dimethylformamide (4 mL) at 25° C. The reaction mixture was stirred at 25° C. for 2 h, and then was partitioned between ethyl acetate (30 mL) and water (2×20 mL). The organic layers were washed with saturated aqueous brine solution (50 mL), dried over sodium sulfate, filtered, and were concentrated in vacuo. The residue was purified by flash column chromatography (Analogix SuperFlash Column; 30-80% ethyl acetate in hexanes) to afford the desired product, N-{3-[4-hydroxy-1-(3-methyl-butyl)-2-oxo-2,4a,5,6,7,8,9,9a-octahydro-1H-cyclohepta[b]pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide (0.045 g, 0.084 mmol, 34%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.00 (d, 6H, J=7.1 Hz), 1.40-2.24 (m, 14H), 2.88 (d, 3H, J=2.1 Hz), 2.94-3.09 (m, 1H), 3.30-3.53 (m, 2H), 3.37 (d, 3H, J=3.1 Hz), 3.95-4.09 (m, 1H), 7.17-7.23 (m, 1H), 7.67-7.73 (m, 1H), 7.77-7.80 (m, 1H). LC-MS (ESI) calcd for C24H34N4O6S2 538.19, found 539.4 [M+H+].

후처리

  1. customwas partitioned between ethyl acetate (30 mL) and water (2×20 mL)
  2. washThe organic layers were washed with saturated aqueous brine solution (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationwere concentrated in vacuo
  6. customThe residue was purified by flash column chromatography (Analogix SuperFlash Column; 30-80% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-fad7d9b5ba7f4873a02d02ef8adee051
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582626B2

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