p-Toluenesulfonic acid → HCID 59560633, compound

HRID 885666Notes

Reaction equation

HRID 885666 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:11](=[CH:12][N:13]([C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH3:29])[N:26]=4)[N:21]=[CH:20][CH:19]=3)[N:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(OC(N1CCC(=O)C(=CO)CC1)=O)(C)(C)C.COC1N=C2C(=CC=1)N=CC=C2NN.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C(Cl)Cl.[OH-].[Na+]>[CH3:29][O:28][C:25]1[N:26]=[C:27]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[C:18]2[N:13]1[CH:12]=[C:11]2[C:15]([CH2:16][CH2:17][NH:8][CH2:9][CH2:10]2)=[N:14]1

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 55280697HCID 55280697, compoundHCID 59560613HCID 59560613, compoundHCID 68498736HCID 68498736, compound

Product 1

HCID 59560633HCID 59560633, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. To a solution of 4-hydroxymethylene-5-oxo-azepane-1-carboxylic acid tert-butyl ester (500 mg, 2.0 mmol) in THF (7 mL) was added (6-methoxy-[1,5]naphthyridin-4-yl)-hydrazine (480 mg, 2.4 mmol). The reaction was stirred at RT for 4 h. Then p-toluenesulfonic acid (600 mg, 6.0 mmol) was added and the reaction was stirred at RT for an additional 12 h. The reaction was diluted with CH2Cl2 (30 mL) and 1 N NaOH (40 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic layers were washed with 1 N NaOH (50 mL), brine (30 mL), dried (MgSO4), filtered and concentrated. The residue was purified on SiO2 (60% EtOAc/hexanes) to afford 510 mg (65%) of the title compound as a pale yellow oil. 1H NMR (7:3 mixture of isomers; 500 MHz, CDCl3): 9.25-9.22 (m, 0.7H), 9.14 (s, 0.3H), 8.75 (d, J=5.0, 1H), 8.27-8.12 (m, 2H), 7.19-7.15 (m, 1H), 4.43-4.39 (m, 1H), 4.12 (s, 3H), 3.71-3.57 (m, 2H), 3.05-2.99 (m, 2H), 2.81-2.79 (m, 0.7H), 1.90-1.87 (m, 1.3H), 1.69-1.65 (m, 1H), 1.50 (s, 3H), 1.40 (s, 6H).

Workup

  1. stirringthe reaction was stirred at RT for an additional 12 h
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (2×20 mL)
  4. washThe combined organic layers were washed with 1 N NaOH (50 mL), brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on SiO2 (60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0bf02c11ab374f0ba074909738d09750
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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