Triethylamine → HCID 58204842, compound

HRID 1629500Notes

Reaction equation

HRID 1629500 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21](O)[N:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[H-].[Na+].[CH:26]12[NH:33][CH:30]([CH2:31][CH2:32]1)[CH2:29][NH:28][C:27]2=[O:34].C(N(CC)CC)C>CN1C(=O)CCC1>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[N:20][C:21]([N:33]5[CH:30]6[CH2:31][CH2:32][CH:26]5[C:27](=[O:34])[NH:28][CH2:29]6)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 124305893,8-diazabicyclo(3.2.1)octan-2-oneHCID 1360309132-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol

Product 1

HCID 58204842HCID 58204842, compoundYield 29.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a suspension of 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol from Example 93 (137 mg, 0.44 mmol) in NMP (1.2 mL) was added sodium hydride (60% in mineral oil, 21 mg, 0.53 mmol). The reaction mixture was stirred at RT for 45 min, then at 45° C. for 45 min then cooled to RT. Phenyl trifluorosulphonimide (189 mg, 0.53 mmol) was added and the reaction stirred at RT for 1 h. 3,8-diaza-bicyclo[3.2.1]octan-2-one (69 mg, 0.48 mmol) and triethylamine (77 μL, 0.44 mmol) were added and the reaction mixture heated at 100° C. for 72 h then 120° C. for 7 h. The reaction mixture was cooled to RT, quenched with water and the resulting solid filtered and dried in vacuo. The resultant solid was loaded onto an Isolute SCX-2 cartridge, washed with methanol and eluted with 2M ammonia in methanol. Basic fractions were combined and concentrated in vacuo, the resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% methanol in DCM) to give 466 (54 mg, 29%). LCMS: RT=2.33 min, [M+H]+=421. 1H NMR 300 MHz (DMSO-d6) δ: 9.13 (1 H, s), 7.88 (2 H, d, J=8.29 Hz), 7.19 (1 H, br, s), 6.42 (1 H, s), 5.95 (1 H, m), 4.53 (4 H, d, J=10.45 Hz), 4.50 (1 H, m), 3.49 (1 H, m), 3.17 (1 H, d, J=5.21 Hz), 2.98 (1 H, m), 2.05-2.20 (2 H, m), 1.99 (1 H, m), 1.95-1.98 (1 H, m), 1.48 (6 H, dd, J=6.57, 2.41 Hz)

Workup

  1. temperatureat 45° C. for 45 min then cooled to RT
  2. additionPhenyl trifluorosulphonimide (189 mg, 0.53 mmol) was added
  3. stirringthe reaction stirred at RT for 1 h
  4. temperaturethe reaction mixture heated at 100° C. for 72 h
  5. wait120° C. for 7 h
  6. temperatureThe reaction mixture was cooled to RT
  7. customquenched with water
  8. filtrationthe resulting solid filtered
  9. customdried in vacuo
  10. washwashed with methanol
  11. washeluted with 2M ammonia in methanol
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-23b60b66a530487ca451ff2cb25fc062
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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