Triethylamine → 1-(4-((5-Fluorobenzo[d]thiazol-2-yl)methyl)piperazin-1-yl)-2-(-4-(4-nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)ethanone

HRID 1772288Notes

Reaction equation

HRID 1772288 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[N:7][C:6]=2[CH:17]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[N+:47]([C:50]1[CH:55]=[CH:54][C:53]([NH:56][CH:57]2[CH2:62][CH2:61][CH:60]([O:63][CH2:64][C:65](O)=[O:66])[CH2:59][CH2:58]2)=[CH:52][C:51]=1[C:68]([F:71])([F:70])[F:69])([O-:49])=[O:48]>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][N:11]3[CH2:16][CH2:15][N:14]([C:65](=[O:66])[CH2:64][O:63][CH:60]4[CH2:61][CH2:62][CH:57]([NH:56][C:53]5[CH:54]=[CH:55][C:50]([N+:47]([O-:49])=[O:48])=[C:51]([C:68]([F:70])([F:69])[F:71])[CH:52]=5)[CH2:58][CH2:59]4)[CH2:13][CH2:12]3)=[N:7][C:6]=2[CH:17]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 623094565-Fluoro-2-(piperazin-1-ylmethyl)-1,3-benzothiazoleHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 867195251-(4-((5-Fluorobenzo[d]thiazol-2-yl)methyl)piperazin-1-yl)-2-(-4-(4-nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)ethanoneYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-fluoro-2-(piperazin-1-ylmethyl)-1,3-benzothiazole (130 mg, 0.52 mmol), EDAC.HCl (149 mg, 0.78 mmol), HOBt (105 mg, 0.78 mmol) and triethylamine (157 mg, 1.55 mmol) in dichloromethane (30 ml) was stirred for 1 hour at room temperature before the addition of 2-(-4-(4-nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid (187 mg, 0.52 mmol). After stirring overnight at room temperature, the solution was diluted with dichloromethane (100 ml) and washed with water (50 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue, which was purified by HPLC to afford 1-(4-((5-fluorobenzo[d]thiazol-2-yl)methyl)piperazin-1-yl)-2-(-4-(4-nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)ethanone as a yellow solid (162.0 mg, 53%). (ES, m/z): [M+H]+ 596.00; 1H NMR (300 MHz, CDCl3): δ 8.01 (d, J=9.0 Hz, 1H), 7.87 (dd, J=8.7, 4.8 Hz, 1H), 7.72 (dd, J=9.0, 2.4 Hz, 1H), 7.29-7.23 (m, 1H), 6.84 (d, J=2.1 Hz, 1H), 6.62 (dd, J=9.0, 2.1 Hz, 1H), 5.52 (br s, 1H), 4.47 (s, 2H), 4.20 (s, 2H), 3.93-3.90 (m, 4H), 3.43-3.33 (m, 2H), 3.22-3.19 (m, 4H), 2.11-2.01 (m, 4H), 1.48-1.37 (m, 2H), 1.32-1.21 (m, 2H).

Workup

  1. washwashed with water (50 ml)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto give a residue, which
  6. customwas purified by HPLC

Sources & evidence

ORD record
ord-019a2ffbb1244e8da7a9d8edd9b81670
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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