1-Hydroxybenzotriazole → HCID 44235504, compound

HRID 1093588Notes

Reaction equation

HRID 1093588 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([NH:14][CH2:15][C:16]([OH:18])=O)=[O:13])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH3:51][N:52]([CH:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[C:59]([F:62])([F:61])[F:60]>CN(C=O)C.O>[CH3:51][N:52]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[C:59]([F:62])([F:60])[F:61])[CH:63]1[CH2:68][CH2:67][N:66]([C:16](=[O:18])[CH2:15][NH:14][C:12]([C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:11][N:10]=2)=[O:13])[CH2:65][CH2:64]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidHCID 66591695N-Methyl-N-(2-(trifluoromethyl)phenyl)piperidin-4-amine hydrochloride

Product 1

HCID 44235504HCID 44235504, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (0.0576 g, 0.00021 mol) in DMF (1 mL), was added DIPEA (0.1317 g, 0.0010 mol), HOBt (0.035 g, 0.00025 mol) and EDCI.HCl (0.049 g, 0.00025 mol) at ambient temperature. After 2 minutes methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride (0.06 g, 0.00021 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product extracted with ethyl acetate. The ethyl acetate layer was collected and washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B), gradient: (Time): (% B)-0:30; 2:50; 8:80)]) to afford 0.015 g (15%) of 5-phenyl-isoxazole-3-carboxylic acid (2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide. LCMS: 487.19 (M+1)+, 98.16%, 1H NMR (DMSO-d6): δ 8.58 (t, 1H), 7.94 (m, 2H), 7.7 (m, 2H), 7.56 (m, 3H), 7.34 (m, 2H), 4.3 (m, 1H), 4.15 (d, 2H), 3.8 (d, 1H), 3.0 (m, 2H), 2.6 (s, 3H), 1.7 (m, 2H), 1.4 (m, 1H), 1.3 (m, 2H).

Workup

  1. extractionthe product extracted with ethyl acetate
  2. customThe ethyl acetate layer was collected
  3. washwashed with brine solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B)

Sources & evidence

ORD record
ord-01e5a09d913c4e659c3257545091586e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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