Water → 2-{2-[4-(8-Fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-2-ylmethyl)piperidino]ethyl}naphtho[1,8-cd]isothiazole 1,1-dioxide

HRID 1196608Notes

Reaction equation

HRID 1196608 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH:16]4[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)[CH2:14][C:5]=3[C:4]=2[CH:3]=1.Cl[CH2:23][CH2:24][N:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[C:33]3[CH:34]=[CH:35][CH:36]=[C:27]([C:28]=23)[S:26]1(=[O:38])=[O:37].C(=O)([O-])O.[Na+].O>CN1CCN(C)C1=O>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH:16]4[CH2:17][CH2:18][N:19]([CH2:23][CH2:24][N:25]5[C:29]6[CH:30]=[CH:31][CH:32]=[C:33]7[CH:34]=[CH:35][CH:36]=[C:27]([C:28]=67)[S:26]5(=[O:38])=[O:37])[CH2:20][CH2:21]4)[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 145800412-(2-Chloroethyl)naphtho[1,8-cd]isothiazole 1,1-dioxideHCID 149955504-(8-fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-2-ylmethyl)piperidine

Product 1

HCID 149955512-{2-[4-(8-Fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-2-ylmethyl)piperidino]ethyl}naphtho[1,8-cd]isothiazole 1,1-dioxideYield 19.4%

Reagents, catalysts & solvents 1

HCID 66611,3-Dimethyl-2-imidazolidinoneSolvent

Procedure

A mixture of 4-(8-fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-2-ylmethyl)piperidine (1 g), 2-(2-chloroethyl)naphtho[1,8-cd]isothiazole 1,1-dioxide (0.94 g) and sodium hydrogen carbonate (0.59 g) in 1,3-dimethyl-2-imidazolidinone (25 cc) is brought to 150° C. for 16 hours. After return to a temperature in the vicinity of 25° C., this solution is poured into water (75 cc) and the mixture is extracted with ethyl acetate (3×75 cc). The combined organic phases are dried over magnesium sulphate and taken to dryness at 80° C. under reduced pressure (20 mm Hg: 2.7 kPa). The residue is purified by flash chromatography on a silica column under nitrogen at moderate pressure (0.5-1.5 bar) with a dichloromethane/methanol mixture (90:10 by volume) as eluent. 2-{2-[4-(8-Fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-2-ylmethyl)piperidino]ethyl}naphtho[1,8-cd]isothiazole 1,1-dioxide (0.35 g), m.p. 228° C., is obtained.

Workup

  1. extractionthe mixture is extracted with ethyl acetate (3×75 cc)
  2. dry with materialThe combined organic phases are dried over magnesium sulphate
  3. customtaken to dryness at 80° C. under reduced pressure (20 mm Hg: 2.7 kPa)
  4. customThe residue is purified by flash chromatography on a silica column under nitrogen at moderate pressure (0.5-1.5 bar) with a dichloromethane/methanol mixture (90:10 by volume) as eluent

Sources & evidence

ORD record
ord-3fea43c29a104ad5945ef34e9e060136
Source dataset
uspto-grants-1992_05
Patent number
US05114949

Reaction notes

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