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 731332Notes

Reaction equation

HRID 731332 reaction equation
[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

Participants

5

Reactant 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

Product 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-methanesulfonamideYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

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+].

Workup

  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)

Sources & evidence

ORD record
ord-fad7d9b5ba7f4873a02d02ef8adee051
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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