Triethylamine → 4-(2-Fluorophenyl)-N-(2-methylbenzothiazol-5-yl)-1-piperazine carboxamide

HRID 491572

Reaction equation

HRID 491572 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH3:10])=[N:7][C:6]=2[CH:11]=1.C(N(CC)CC)C.ClC(Cl)(O[C:23](=[O:29])OC(Cl)(Cl)Cl)Cl.[F:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>C(Cl)Cl>[F:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[N:38]1[CH2:43][CH2:42][N:41]([C:23]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[S:9][C:8]([CH3:10])=[N:7][C:6]=3[CH:11]=2)=[O:29])[CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 362295-Benzothiazolamine, 2-methyl-HCID 705291-(2-Fluorophenyl)piperazineHCID 94429Triphosgene

Product 1

HCID 100905614-(2-Fluorophenyl)-N-(2-methylbenzothiazol-5-yl)-1-piperazine carboxamideYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-amino-2-methylbenzothiazole (100 mg, 0.61 mmol) and triethylamine (170 ul, 1.22 mmol) in DCM (5 ml) at 0° C. under an argon atmosphere was added triphosgene (60 mg, 0.2 mmol). The mixture was warmed to room temp. and stirred for 1 h. 4-(2-Fluorophenyl)piperazine (110 mg, 0.61 mmol) was added and the reaction was stirred at room temp. overnight. The solvent was removed in vacuo and the residue purified by chromatography eluting with a 0-100% EtOAc/petroleum ether gradient to give the title compound as a pale yellow solid (69 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.82 (d, 1H), 7.71 (d, 1H), 7.53 (dd, 1H), 6.92-7.10 (m, 4H), 6.65 (s, 1H), 3.69 (m, 2H), 3.13 (m, 2H), 2.81 (s, 3H). MS(ES): MH+ 371, M−H+ 369.

Workup

  1. temperatureThe mixture was warmed to room temp.
  2. stirringthe reaction was stirred at room temp. overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue purified by chromatography
  5. washeluting with a 0-100% EtOAc/petroleum ether gradient

Sources & evidence

ORD record
ord-157e463f7efb4d5b9ea527d9ddd05e0f
Source dataset
uspto-grants-2009_05
Patent number
US07531558B2

Linked notes

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