1-Hydroxybenzotriazole → 1-[(6-Chloro-3-pyridinyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine

HRID 43426Notes

Reaction equation

HRID 43426 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[F:42][C:43]([F:60])([F:59])[C:44]1[CH:49]=[CH:48][C:47]([S:50]([N:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)(=[O:52])=[O:51])=[CH:46][CH:45]=1>C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:56]2[CH2:55][CH2:54][N:53]([S:50]([C:47]3[CH:46]=[CH:45][C:44]([C:43]([F:59])([F:60])[F:42])=[CH:49][CH:48]=3)(=[O:51])=[O:52])[CH2:58][CH2:57]2)=[O:8])=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 792226-Chloronicotinic acidHCID 81531DiisopropylethylamineHCID 25545781-[4-(Trifluoromethyl)benzenesulfonyl]piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 244008621-[(6-Chloro-3-pyridinyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazineYield 49.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 6-chloro nicotinic acid (1.76 g, 11.2 mmol) in DCM (50 ml) at 0° C. was added EDC.HCl (2.93 g, 15.3 mmol), HOBt (2.34 g, 15.3 mmol) and DIPEA (7.52 ml, 40.8 mmol) and the mixture stirred for 20 min. 1-{[4-(Trifluoromethyl)phenyl]sulfonyl}piperazine (may be prepared as described in Description 1) (3.00 g, 10.2 mmol) was added and the solution allowed to warm to room temperature, then stirred overnight. The mixture was diluted with DCM (20 ml), washed with water (5×20 ml), then the organic layers dried (Na2SO4) and concentrated under vacuum to leave the crude compound. Flash chromatography (silica; 60% EtOAc in pet. ether) gave the title compound as a white solid (2.20 g).

Workup

  1. stirringstirred overnight
  2. washwashed with water (5×20 ml)
  3. dry with materialthe organic layers dried (Na2SO4)
  4. concentrationconcentrated under vacuum
  5. customto leave the crude compound

Sources & evidence

ORD record
ord-2235a20d343a41169bcc6156991ef1dc
Source dataset
uspto-grants-2013_09
Patent number
US08536183B2

Reaction notes

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