1-Aminopiperidine → HCID 59485715, compound

HRID 1972266Notes

Reaction equation

HRID 1972266 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([F:23])[CH:14]=3)[C@H:11]([CH2:24][N:25]3[CH:29]=[C:28]([C:30]([OH:32])=O)[N:27]=[N:26]3)[O:10][C:9]2=[O:33])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:67][N:68]1[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]1>CC#N>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[C:17]([C:19]([F:21])([F:22])[F:20])[CH:16]=[C:15]([F:23])[CH:14]=3)[C@H:11]([CH2:24][N:25]3[CH:29]=[C:28]([C:30]([NH:67][N:68]4[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]4)=[O:32])[N:27]=[N:26]3)[O:10][C:9]2=[O:33])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 166581-AminopiperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59485902HCID 59485902, compound

Product 1

HCID 59485715HCID 59485715, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(4S,5S)-1-((3-(4-Chlorophenyl)-4-(3-fluoro-5-(trifluoromethyl)phenyl)-2-oxooxazolidin-5-yl)methyl)-1H-1,2,3-triazole-4-carboxylic acid (40 mg, 0.082 mmol) is dissolved in CH3CN (2 mL) and is successively treated with DIEA (14 μL, 0.082 mmol) and HATU (31 mg, 0.082 mmol) at ambient temperature. After 5 minutes, 1-aminopiperidine (10 μL, 0.097 mmol) is added and the reaction stirred for 2 h as judged complete by LC-MS. The reaction is quenched with 1 mL 1M HCl and diluted with water and ethyl acetate. The organic layer is washed successively with NaHCO3, brine, dried over MgSO4, filtered and concentrated. Purification by flash chromatography on silica gel (0-5% methanol/dichloromethane) gives the title compound (17 mg, 37%) as a white film. 1H NMR (acetone-d6, 400 MHz) δ 8.49 (s, 1H), 8.39 (s, 1H), 7.72 (s, 1H), 7.66 (d, 1H, J=9.2 Hz), 7.52 (d, 1H, J=8.5 Hz), 7.45-7.49 (m, 2H), 7.30-7.33 (m, 2H), 5.85 (d, 1H, J=5.5 Hz), 5.21 (d, 2H, J=5.6 Hz), 5.11 (q, 1H, J=5.6 Hz), 2.89 (t, 4H, J=5.3 Hz), 1.65 (pentet, 4H, J=6.0 Hz), 1.48-1.51 (m, 1H), 1.39-1.45 (m, 1H). HPLC-MS calculated C25H23ClF4N6O3 (M+H+): 567.2, found: 567.2.

Workup

  1. customThe reaction is quenched with 1 mL 1M HCl
  2. additiondiluted with water and ethyl acetate
  3. washThe organic layer is washed successively with NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica gel (0-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-1d0a4c6bf5584e60908a4886a0fb7f59
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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