Triethylamine → HCID 59000960, compound

HRID 1893841Notes

Reaction equation

HRID 1893841 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C@H:19]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:20]([NH2:22])=[O:21])[CH2:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCN(CC)CC.Cl.[C:35](Cl)(=[O:42])[C:36]1[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C@H:19]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:20]([NH2:22])=[O:21])[CH2:12][CH:13]2[CH2:14][CH2:15][N:16]([C:35]([C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)=[O:42])[CH2:17][CH2:18]2)(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 12262826Isonicotinoyl chloride hydrochlorideHCID 59001103(2R)-2-[N-(4-Chlorobenzenesulfonyl)-N-(piperidin-4-ylmethyl)amino]-4-methyl-pentanoic acid amide

Product 1

HCID 59000960HCID 59000960, compoundYield 32.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R)-2-[N-(4-chlorobenzenesulfonyl)-N-(piperidin-4-ylmethyl)amino]-4-methyl-pentanoic acid amide (Example 126, 0.10 g, 0.22 mmol) and Et3N (0.06 mL, 0.5 mmol) in CH2Cl2 (3.0 mL) was added isonicotinoyl chloride hydrochloride (56 mg, 0.32 mmol). The reaction was stirred at rt for 18 h and then was poured into a mixture of EtOAc and sat. aq. NaHCO3. The organic solution was separated and washed with brine, dried over MgSO4, and concentrated to an oily residue. The residue was purified on a BIOTAGE® 10M (eluted with 80% EtOAc/hexanes) to give a white solid (36 mg, 30%). MS (ESI), (M+H)+509.20; 1H NMR (CDCl3, 500 MHz) δ 8.66 (br s, 2H), 7.80 (d, 1H, J=8.6), 7.73 (d, 2H, J=8.5), 7.51 (d, 2H, J=7.6), 7.41 (br s, 1H), 6.64 (br s, 1H), 5.35 (br s, 1H), 4.70 (br s, 1H), 4.10 (br s, 1H), 3.71 (br s, 1H), 3.33 (br s, 1H), 3.02 (dd, 2H, J=4.8, 16), 2.70-2.85 (br s, 1H), 1.50-2.09 (m, 5H), 1.18-1.33 (m, 4H), 0.73 (d, 3H, J=6.7), 0.68 (d, 3H, J=6.5).

Workup

  1. customThe organic solution was separated
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated to an oily residue
  5. customThe residue was purified on a BIOTAGE® 10M (eluted with 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d79137d6ff4f41979c240589ed8a7d25
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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