Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1) → 4-(2-(1-Methylpyrrolidin-2-yl)ethyl)-7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine

HRID 424506

反応式

HRID 424506 の反応式
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[NH:12][CH2:11][CH2:10][S:9][C:8]=2[CH:13]=1)([O-:3])=[O:2].Cl.Cl[CH2:16][CH2:17][CH:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH3:23]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.[OH-].[Na+].O>[CH3:23][N:19]1[CH2:20][CH2:21][CH2:22][CH:18]1[CH2:17][CH2:16][N:12]1[CH2:11][CH2:10][S:9][C:8]2[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]1=2

参加物

7

反応物 2

HCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)HCID 204961217-Nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine

生成物 1

HCID 591440834-(2-(1-Methylpyrrolidin-2-yl)ethyl)-7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine収率 52.8%

試薬・触媒・溶媒 4

HCID 74236Tetrabutylammonium Bromide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 14798Sodium Hydroxide溶媒

実験手順

A mixture of 7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine (1 g, 5.10 mmol), 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (1.876 g, 10.19 mmol), and tetrabutylammonium bromide (0.082 g, 0.255 mmol) in dichloromethane (10 mL) and 50% NaOH solution (10 mL) was stirred at room temperature for 16 hours (overnight). The reaction was then diluted with dichloromethane (5 mL) and water (20 mL), and the mixture was transferred to a separatory funnel. The organic layer was removed, and the aqueous layer was extracted into dichloromethane (2×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The red crude material was subjected to column chromatography on silica gel using the Biotage purification system (80 g silicycle column; gradient: dichloromethane 3CV then ramp to 6:94 (2M NH3 in methanol):dichloromethane over 15CV; 254 nm; flow: 45 mL/min) to give the title compound as yellow-orange solid (0.827 g, 52.8%). 1H-NMR (DMSO-d6) δ 7.87 (dd, J=3.0, 9.0 Hz, 1H), 7.83 (d, J=3.0 Hz, 1H), 6.79 (d, J=9.3 Hz, 1H), 3.79-3.76 (m, 2H), 3.46 (t, J=8.1 Hz, 2H), 3.08-3.05 (m, 2H), 2.99-2.92 (m, 1H), 2.23 (s, 3H), 2.10-2.06 (m, 2H), 1.92-1.78 (m, 2H), 1.66-1.61 (m, 2H), 1.54-1.47 (m, 2H); ESI-MS (m/z, %): 308 (MH+, 100).

後処理

  1. customthe mixture was transferred to a separatory funnel
  2. customThe organic layer was removed
  3. extractionthe aqueous layer was extracted into dichloromethane (2×10 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe Biotage purification system (80 g silicycle column

出典と根拠

ORDレコード
ord-04966b1728184519bae6295573f25a9c
出典データセット
uspto-grants-2012_01
特許番号
US08106043B2

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