1-Hydroxybenzotriazole → Benzyl 4-((3-chloropyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate

HRID 550127Notes

Reaction equation

HRID 550127 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:5]([CH2:10][NH2:11])=[N:6][CH:7]=[CH:8][N:9]=1.C(N(CC)C(C)C)(C)C.CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.[CH2:43]([O:50][C:51]([N:53]1[CH2:58][CH2:57][CH:56]([C:59](O)=[O:60])[CH2:55][CH2:54]1)=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(Cl)Cl>[Cl:3][C:4]1[C:5]([CH2:10][NH:11][C:59]([CH:56]2[CH2:57][CH2:58][N:53]([C:51]([O:50][CH2:43][C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)=[O:52])[CH2:54][CH2:55]2)=[O:60])=[N:6][CH:7]=[CH:8][N:9]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 42609650(3-Chloropyrazin-2-yl)methanamine dihydrochloride

Product 1

HCID 42609366Benzyl 4-((3-chloropyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of C-(3-Chloropyrazin-2-yl)methylamine bis-hydrochloride (2.00 g, 0.0107 mol) and N,N-diisopropylethylamine (2.2 g, 0.017 mol) in DCM (27.0 mL) was treated with and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (3.2 g, 0.017 mol), 1-hydroxybenzotriazole (1.5 g, 0.011 mol) and 1-[(benzyloxy)carbonyl]-4-piperidine carboxylic acid (3.8 g, 0.014 mol). The mixture was stirred at rt overnight then diluted with DCM (30 mL), washed with sat. NaHCO3(20 mL) and brine (20 mL), then dried over Na2SO4 and concentrated in vacuo. The crude material thus obtained was chromatographed over silica gel eluting with EtOAc:hexane 1:1 yielding 3.38 g of the title compound. 1H NMR (400 MHz, CDCl3): δ 1.68-1.78 (m, 2H), 1.91-1.94 (m, 2H), 2.44 (m, 1H), 2.89-2.92 (m, 2H), 4.24-4.26 (m, 2H), 4.70 (d, J=4.8 Hz, 2H), 5.14 (s, 2H), 6.85 (br, 1H), 7.30-7.37 (m, 5H), 8.34 (d, J=2.8 Hz, 1H), 8.45 (d, J=2.8 Hz, 1H). MS (ES+): m/z 389.17 [MH+].

Workup

  1. washwashed with sat. NaHCO3(20 mL) and brine (20 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9857e694d6b44ac681eb9324b0fc1fca
Source dataset
uspto-grants-2011_05
Patent number
US07943767B2

Reaction notes

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