Triethylamine → 1-{3-[(1-Oxido-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-yl)amino]propyl}-3-pyrrolidinecarbonitrile

HRID 1669045Notes

Reaction equation

HRID 1669045 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH:7]([C:10]#[N:11])[CH2:6]1.Cl[C:13]1[N:14]=[N+:15]([O-:26])[C:16]2[CH:25]=[C:24]3[C:20]([CH2:21][CH2:22][CH2:23]3)=[CH:19][C:17]=2[N:18]=1.CCN(CC)CC>COCCOC>[O-:26][N+:15]1[C:16]2[CH:25]=[C:24]3[C:20](=[CH:19][C:17]=2[N:18]=[C:13]([NH:1][CH2:2][CH2:3][CH2:4][N:5]2[CH2:9][CH2:8][CH:7]([C:10]#[N:11])[CH2:6]2)[N:14]=1)[CH2:21][CH2:22][CH2:23]3

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 160813203-Chloro-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1-OxideHCID 574476861-(3-Aminopropyl)-3-pyrrolidinecarbonitrile

Product 1

HCID 119514641-{3-[(1-Oxido-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-yl)amino]propyl}-3-pyrrolidinecarbonitrileYield 78.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

1-(3-Aminopropyl)-3-pyrrolidinecarbonitrile (302) (0.36 g, 2.4 mmol) was added to a stirred solution of chloride 21 (402 mg, 1.8 mmol) and Et3N (0.76 mL, 5.4 mmol) in DME (50 mL) and the solution stirred at reflux temperature for 16 h. The solvent was evaporated and the residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL). The organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1-oxide 56 (476 mg, 78%) as a yellow solid: mp (EtOAc/pet. ether) 111-112° C.; 1H NMR δ 8.07 (s, 1H, H-9), 7.39 (s, 1H, H-5), 5.72 (br t, J=5.3 Hz, 1H, NH), 3.58 (q, J=6.4 Hz, 2H, CH2N), 2.95-3.07 (m, 6H, H-6, H-8, CH2N), 2.73-2.80 (m, 1H, CHCN), 2.55-2.68 (m, 4H, 2×CH2), 2.23-2.32 (m, 1H, CH2), 2.10-2.18 (m, 3H, CH2, H-7), 1.85 (p, J=6.7 Hz, 2H, CH2); 13C NMR δ 158.7, 154.6, 148.7, 143.3, 129.8, 122.1, 120.6, 114.6, 57.4, 53.3, 52.9, 40.2, 33.1, 32.3, 29.2, 27.7, 26.3, 25.7. Anal. calcd for C18H22N6O: C, 63.9; H, 6.6; N, 24.8. Found: C, 64.0; H, 6.4; N, 24.8%.

Workup

  1. temperatureat reflux temperature for 16 h
  2. customThe solvent was evaporated
  3. customthe residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL)
  4. customThe organic fraction was dried
  5. customthe solvent evaporated
  6. customThe residue was purified by chromatography
  7. washeluting with a gradient (0-10%) of MeOH/DCM

Sources & evidence

ORD record
ord-da25842bf350435cbcfdc0718763fd6a
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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