Triethylamine → HCID 9808382, compound

HRID 497452Notes

Reaction equation

HRID 497452 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[CH:42]=[C:43]([N:47]=[C:48]=[O:49])[CH:44]=[CH:45][CH:46]=1)(=[O:40])[CH3:39]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:48]([NH:47][C:43]2[CH:44]=[CH:45][CH:46]=[C:41]([C:38](=[O:40])[CH3:39])[CH: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

5

Reactant 3

HCID 8471TriethylamineHCID 3127181-(3-Isocyanatophenyl)ethan-1-oneHCID 69748878HCID 69748878, compound

Product 1

HCID 9808382HCID 9808382, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 (56 mg, 0.133 mmol) was dissolved in tetrahydrofuran (2 mL) and triethylamine (24 μL, 0.172 mmol) and 3-acetylphenylisocyanate (22 μL, 0.160 mmol) were added. The reaction mixture was stirred for 17 hours. One-half of the original reaction mixture (1 mL) was concentrated in vacuo then purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid) to give a white amorphous solid (24 mg, 62%). 1H NMR (400 MHz, DMSO, 120° C.), δ: 8.32 (s, 1H), 7.91 (t, 1H, J=2), 7.58 (m, 1H), 7.48 (m, 1H), 7.33 (t, 1H, J=8), 7.15 (m, 2H), 6.99 (m, 2H), 5.98 (d, 1H, J=10), 4.04 (bd, 1H, J=13), 3.89 (bm, 4H), 3.20 (bs, 2H), 2.96 (m, 2H), 2.86 (m, 2H), 2.50 (s, 3H), 2.46 (m, 2H), 1.90 (m, 1H), 1.62 (bm, 4H), 1.43 (2s, 9H), 1.20 (m, 1H). HRMS (ESI), C32H42FN4O5 m+/z: calc.=581.3139, found=581.3141.

Workup

  1. concentrationOne-half of the original reaction mixture (1 mL) was concentrated in vacuo
  2. customthen purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-069a7402132749a8950fcf4df3ff0b8e
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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