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

HRID 1878871Notes

Reaction equation

HRID 1878871 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.ON1C2C=CC=CC=2N=N1.[CH2:31]([O:38][C:39]([N:41]1[CH2:46][CH2:45][CH:44]([C:47](O)=[O:48])[CH2:43][CH2:42]1)=[O:40])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)Cl>[Cl:3][C:4]1[C:5]([CH2:10][NH:11][C:47]([CH:44]2[CH2:45][CH2:46][N:41]([C:39]([O:38][CH2:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[O:40])[CH2:42][CH2:43]2)=[O:48])=[N:6][CH:7]=[CH:8][N:9]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic AcidHCID 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)-Al-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-64979d74cc5c45509d22f8dc9dd9f600
Source dataset
uspto-grants-2012_11
Patent number
US08314111B2

Reaction notes

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