2-methyl-5-[[(2S)-oxiran-2-yl]methoxy]-1,3-benzothiazole → (2S)-3-((2S)-4-{[5-(2-fluorophenyl)isoxazol-3-yl]methyl}-2-methylpiperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-ol

HRID 891052Notes

Reaction equation

HRID 891052 reaction equation
[CH3:1][C@@H:2]1[NH:7][CH2:6][CH2:5][N:4]([CH2:8][C:9]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[O:11][N:10]=2)[CH2:3]1.[O:21]1[CH2:23][C@H:22]1[CH2:24][O:25][C:26]1[CH:27]=[CH:28][C:29]2[S:33][C:32]([CH3:34])=[N:31][C:30]=2[CH:35]=1>C(O)(CC)(C)C>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:12]1[O:11][N:10]=[C:9]([CH2:8][N:4]2[CH2:5][CH2:6][N:7]([CH2:23][C@H:22]([OH:21])[CH2:24][O:25][C:26]3[CH:27]=[CH:28][C:29]4[S:33][C:32]([CH3:34])=[N:31][C:30]=4[CH:35]=3)[C@@H:2]([CH3:1])[CH2:3]2)[CH:13]=1

Participants

4

Reactant 2

HCID 235989442-methyl-5-[[(2S)-oxiran-2-yl]methoxy]-1,3-benzothiazoleHCID 69600490(3S)-1-{[5-(2-Fluorophenyl)-1,2-oxazol-3-yl]methyl}-3-methylpiperazine

Product 1

HCID 58595331(2S)-3-((2S)-4-{[5-(2-fluorophenyl)isoxazol-3-yl]methyl}-2-methylpiperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-olYield 38.3%

Reagents, catalysts & solvents 1

HCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
95 °C

Procedure

To a stirred solution of (2S)-methylpiperazine (40 mg, 0.40 mmol) in ethanol (5 mL) was added 3-chloromethyl-5-(2-fluorophenyl)isoxazole (42 mg, 0.20 mmol) and triethylamine (60μL, 0.43 mmol). The resulting mixture was stirred at 80° C. for 8 hours. It was then cooled, concentrated, and purified by preparative chromatography (1:9 methanol:methylene chloride) to yield 3-[((3S)-3-methylpiperazinyl)methyl]-5-(2-fluorophenyl)isoxazole (30 mg, M+1=276.14). B. To a solution of 3-[((3S)-3-methylpiperazinyl)methyl]-5-(2-fluorophenyl)isoxazole (28 mg, 0.10 mmol) in tert-amylalcohol (5 mL) was added 5-[((2S)oxiran-2-yl)methoxy]-2-methylbenzothiazole (22 mg, 0.10 mmol). The reaction mixture was stirred at 95° C. for 1 day. It was then cooled, concentrated, and purified by preparative chromatography (1:19 methanol:methylene chloride) to afford (2S)-3-((2S)-4-{[5-(2-fluorophenyl)isoxazol-3-yl]methyl}-2-methylpiperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-ol (19 mg, M+1=497.27).

Workup

  1. temperatureIt was then cooled
  2. concentrationconcentrated
  3. custompurified by preparative chromatography (1:19 methanol:methylene chloride)

Sources & evidence

ORD record
ord-175c079941dc45f3beb071d6bb7a7a09
Source dataset
uspto-grants-2006_02
Patent number
US07001909B2

Reaction notes

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