4-Methylmorpholine → HCID 86719498, compound

HRID 1772263Notes

Reaction equation

HRID 1772263 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19]([OH:21])=O)[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:22]([F:25])([F:24])[F:23])([O-:3])=[O:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.[CH3:56][C@H:57]1[CH2:62][NH:61][C@H:60]([CH3:63])[CH2:59][N:58]1[CH2:64][C:65]1[S:66][C:67]2[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][C:68]=2[N:69]=1>CN(C=O)C.CCOC(C)=O>[CH3:63][C@@H:60]1[CH2:59][N:58]([CH2:64][C:65]2[S:66][C:67]3[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:75])[F:76])=[CH:70][C:68]=3[N:69]=2)[C@@H:57]([CH3:56])[CH2:62][N:61]1[C:19](=[O:21])[CH2:18][O:17][CH:14]1[CH2:15][CH2:16][CH:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:22]([F:24])([F:25])[F:23])[CH:6]=2)[CH2:12][CH2:13]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acidHCID 86719499HCID 86719499, compound

Product 1

HCID 86719498HCID 86719498, compoundYield 53.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-acetic acid (172 mg, 0.476 mmol, 2 eq.) in DMF (5 ml) was added EDAC hydrochloride (68 mg, 0.36 mmol, 1.5 eq.), HOBt (55 mg, 0.36 mmol, 1.5 eq.) and 4-methylmorpholine (0.13 ml, 1.2 mmol, 5 eq.). The resulting solution was stirred for 30 min then 2-((2S,5R)-2,5-dimethyl-piperazin-1-ylmethyl)-5-trifluoromethyl-benzothiazole hydrochloride (87 mg, 0.24 mmol, 1 eq.) was added. The solution was stirred overnight at room temperature and diluted with EtOAc (25 ml) and washed with water (25 ml), saturated aqueous lithium chloride (25 ml) and brine (25 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue, which was applied onto a silica gel column with Heptanes—EtOAc to afford 1-[(2R,5S)-2,5-dimethyl-4-(5-trifluoromethyl-benzothiazol-2-ylmethyl)-piperazin-1-yl]-2-[4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-ethanone as a yellow solid (86.1 mg, 53.7%). (CI, m/z): [M+H]+ 674; 1H NMR (400 MHz, CDCl3) δ 1.02-1.53 (m, 10H), 2.18 (br s, 4H), 2.47 (d, J=11.7 Hz, 1H), 2.99 (d, J=8.8 Hz, 1H), 3.23 (br s, 1H), 3.31-3.53 (m, 2H), 3.85-4.13 (m, 4H), 4.20 (br s, 3H), 4.46 (d, J=7.6 Hz, 1H), 6.64 (dd, J=9.1, 2.5 Hz, 1H), 6.85 (d, J=2.2 Hz, 1H), 7.63 (d, J=8.3 Hz, 1H), 8.01 (t, J=8.3 Hz, 2H), 8.21 (s, 1H).

Workup

  1. stirringThe solution was stirred overnight at room temperature
  2. washwashed with water (25 ml), saturated aqueous lithium chloride (25 ml) and brine (25 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto give a residue, which

Sources & evidence

ORD record
ord-73507ff8a7e046409b34745a85839516
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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