Triethylamine → HCID 86759180, compound

HRID 1169210Notes

Reaction equation

HRID 1169210 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH2:14])[C@H:10]([C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:18]2)=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:38]([C:41]1[N:42](C)[CH:43]([NH:46][C:47]([O:49]C2C=CC=CC=2)=O)[S:44][CH:45]=1)(=O)C.[C:57](OCC)(=[O:59])[CH3:58]>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:47]([NH:46][C:43]2[S:44][C:45]([C:57](=[O:59])[CH3:58])=[C:41]([CH3:38])[N:42]=2)=[O:49])[C@H:10]([C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:18]2)=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 22318219HCID 22318219, compoundHCID 69748878(3R,4R)-4-amino-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidine-1-carboxylic acid t-butyl ester

Product 1

HCID 86759180HCID 86759180, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

In a dry flask (3R,4R)-4-Amino-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidine-1-carboxylic acid t-butyl ester (73 mg, 0.174 mmol) was dissolved in acetonitrile (2 mL) and triethylamine (25 μL, 0.179 mmol) and 4-acetyl-3-methyl-2-(phenoxycarbonylamino)-thiazole (58 mg, 0.21 mmol) were added. The reaction mixture was stirred for 64 hours while heating to 60° C. The reaction mixture was cooled, diluted with ethyl acetate, washed twice with water and once with brine. The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid) to give a white amorphous solid (60 mg, 57%). 1H NMR (300 MHz, CDCl3), δ: 7.14 (m, 1H), 6.98 (m, 2H), 6.88 (t, 1H, J=10), 4.39 (d, 1H, J=13), 4.09 (bs, 2H), 3.94 (bm, 2H), 3.12 (t, 1H, J=11), 2.74 (bm, 5H), 2.62 (m, 3H), 2.52 (m, 1H), 2.47 (m, 3H), 2.36 (m, 2H), 2.03 (bm, 3H), 1.74 (bm, 2H), 1.48 (2s, 9H), 1.40 (m, 1H), 1.22 (m, 1H). HRMS (ESI), C30H41FN5O5S m+/z: calc.=602.2813, found=602.2811.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed twice with water and once with brine
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-ec90d96fb5c0476286dd943d0990fb4c
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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