1-Hydroxybenzotriazole → HCID 66624895, compound

HRID 1665628Notes

Reaction equation

HRID 1665628 reaction equation
C1C=CC2N(O)N=[N:7][C:5]=2C=1.CCN(C(C)C)C(C)C.[O:20]=[C:21]([N:26]1[CH2:31][CH2:30][N:29]([C:32](=[O:43])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[C:39]([F:42])([F:41])[F:40])[CH2:28][CH2:27]1)[CH2:22][C:23]([OH:25])=O.CCN=C=NCCCN(C)C.Cl.[CH2:56]([O:63][C:64]1N=C[C:67]([NH2:70])=[CH:66][CH:65]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>CN(C=O)C.O>[CH2:56]([O:63][C:64]1[CH:65]=[CH:66][C:67]([NH:70][C:23](=[O:25])[CH2:22][C:21](=[O:20])[N:26]2[CH2:27][CH2:28][N:29]([C:32](=[O:43])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:39]([F:40])([F:42])[F:41])[CH2:30][CH2:31]2)=[N:7][CH:5]=1)[C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5632866-(benzyloxy)pyridin-3-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 578758113-Oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionic acid

Product 1

HCID 66624895HCID 66624895, compoundYield 39.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (43 mg, 0.32 mmol) and DIEA (150 mg, 011 mmol) were added to a stirred solution of 3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionic acid (100 mg, 0.29 mmol) in DMF (4 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (111 mg, 0.58 mmol) followed by 6-benzyloxy-pyridin-3-ylamine (81 mg, 0.4 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water and the product extracted with ethyl acetate. The organics were washed with brine solution, dried over Na2SO4 and concentrated to afford a residue which was purified by column chromatography using silica gel 60-120 mesh (80% ethyl acetate in hexane) to afford 60 mg (39%) of N-(5-benzyloxy-pyridin-2-yl)-3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamide. LCMS: 527.19 (M+1)+, 98.6%, 1H NMR: (DMSO-d6): δ 10.2 (td, 1H), 8.4 (dd, 1H), 8 (dt, 1H), 7.8 (d, 1H), 7.7 (t, 1H), 7.6 (t, 1H), 7.5 (d, 1H), 7.4 (m, 5H), 6.9 (m, 1H), 5.4 (d, 2H), 3.8 (m, 6H), 3.5 (m, 2H), 3.2 (m, 2H).

Workup

  1. additionwere added
  2. extractionthe product extracted with ethyl acetate
  3. washThe organics were washed with brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto afford a residue which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-03b71a6ce32e494185fc753d6d949243
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

Loading…