Aniline → HCID 66558330, compound

HRID 1530500Notes

Reaction equation

HRID 1530500 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]=[CH:21][C:20]([S:23]([O-:26])(=O)=[O:24])=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[Na+].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[C:39]1([NH2:45])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.CCN(CC)CC>C1COCC1.C(Cl)Cl>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[C:20]([S:23]([NH:45][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)(=[O:26])=[O:24])[CH:21]=[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

8

Reactant 5

HCID 6115AnilineHCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 86671459HCID 86671459, compound

Product 1

HCID 66558330HCID 66558330, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfonate from Example 121 (0.26 mmol) in THF (10 mL) was added oxalyl chloride (111 μL, 1.30 mmol) and the resulting mixture stirred at RT for 10 min then cooled to 0° C. before DMF (100 μL, 1.27 mmol) was added. The resulting mixture was stirred for 3 h then azeotroped with toluene. The resulting residue was suspended in DCM (10 mL) and added to a solution of phenylamine (36 μL, 0.39 mmol) and NEt3 (72 μL, 0.52 mmol) in DCM (5 mL) at RT The resulting mixture was stirred for 16 h then quenched with H2O. The organic phase was washed with brine then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-14% MeOH in MeOAc) then freeze-dried from MeCN and H2O affording 118 as a white solid (6 mg, 5%). LCMS: RT 4.18 [M+H]+ 451.2. 1H NMR (DMSO, 400 MHz): δ 8.84 (1H, d, J=2.45 Hz), 7.95 (1H, s), 7.93 (1H, d, J=0.63 Hz), 7.65 (1H, dd, J=8.68, 2.47 Hz), 7.17-7.16 (5H, m), 6.99 (1H, t, J=7.29 Hz), 5.69-5.68 (1H, m), 4.55-4.54 (4H, m), 1.50 (6H, d, J=6.60 Hz)

Workup

  1. additionwas added
  2. stirringThe resulting mixture was stirred for 3 h
  3. customthen azeotroped with toluene
  4. stirringwas stirred for 16 h
  5. customthen quenched with H2O
  6. washThe organic phase was washed with brine
  7. dry with materialthen dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-14% MeOH in MeOAc)
  10. dry with materialthen freeze-dried from MeCN and H2O affording 118 as a white solid (6 mg, 5%)
  11. customRT 4.18 [M+H]+ 451.2

Sources & evidence

ORD record
ord-a8f9ca541a324fcb8b770c10995fb3d5
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…