4-Methylmorpholine → HCID 53252745, compound

HRID 1916434Notes

Reaction equation

HRID 1916434 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]2([C:30]([F:33])([F:32])[F:31])[O:17][N:16]=[C:15]([C:18]3[N:19]4[C:23]([C:24]([C:27]([OH:29])=O)=[CH:25][CH:26]=3)=[CH:22][CH:21]=[CH:20]4)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:66][CH2:67][C:68]([NH:70][CH2:71][C:72]([F:75])([F:74])[F:73])=[O:69]>CN(C=O)C.C(Cl)Cl.O.CC(=O)OCC>[F:73][C:72]([F:75])([F:74])[CH2:71][NH:70][C:68]([CH2:67][NH:66][C:27]([C:24]1[C:23]2[N:19]([CH:20]=[CH:21][CH:22]=2)[C:18]([C:15]2[CH2:14][C:13]([C:5]3[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([C:2]([F:35])([F:34])[F:1])[CH:4]=3)([C:30]([F:33])([F:32])[F:31])[O:17][N:16]=2)=[CH:26][CH:25]=1)=[O:29])=[O:69]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 247051432-Amino-N-(2,2,2-trifluoroethyl)acetamideHCID 86654750HCID 86654750, compound

Product 1

HCID 53252745HCID 53252745, compoundYield 17.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

5-[5-(3,5-Bistrifluoromethylphenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-indolizine-8-carboxylic acid (50 mg), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC.HCl, 22.5 mg), 1-hydroxybenzotriazole monohydrate (HOBt.H2O, 20 mg) and N-methylmorpholine (22 μL) were stirred in a mixture of DMF-DCM (½, 1 mL) for 20 minutes at room temperature prior to adding 2-amino-N-(2,2,2-trifluoroethyl)acetamide (50 mg, Ukrorgsynthesis Ltd. Kiev, UKRAINE). The reaction mixture was stirred overnight at room temperature. The mixture was diluted with water and EA. The organic layer was collected, washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a residue that was purified by chromatography (SiO2, DCM/MeOH) to afford the title compound as an orange-reddish solid (11.1 mg, 17%). MS (ES): M/Z [M+H]=649. 1H NMR (400 MHz, CHLOROFORM-d): 3.88-4.04 (m, 3H), 4.33 (d, J=5.3 Hz, 2H), 4.39 (d, J=16.6 Hz, 1H), 6.84 (d, J=7.4 Hz, 1H), 7.05-7.08 (m, 1H), 7.08-7.21 (m, 3H), 7.33 (t, J=4.9 Hz, 1H), 8.01 (s, 1H), 8.13 (s, 2H), 8.72 (d, J=1.8 Hz, 1H). 19F NMR (376 MHz, CHLOROFORM-d): −80.0 (s, 3F), −72.9 (t, J=9.2 Hz, 3F), −63.3 (s, 6F).

Workup

  1. customThe organic layer was collected
  2. washwashed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue that
  7. customwas purified by chromatography (SiO2, DCM/MeOH)

Sources & evidence

ORD record
ord-f6456aa4860a4b57b3adafc2372b26a7
Source dataset
uspto-grants-2013_12
Patent number
US08618126B2

Reaction notes

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