Dimethylformamide → HCID 66558414, compound

HRID 1530506Notes

Reaction equation

HRID 1530506 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-])(=[O:25])=[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]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)([CH3:42])([CH3:41])[CH3:40].CCN(CC)CC>C1COCC1.C(Cl)Cl>[C:39]([N:43]1[CH2:48][CH2:47][N:46]([S:23]([C:20]2[CH:21]=[CH:22][C:15]3[O:14][CH2:13][CH2:12][N:11]4[CH:10]=[C:9]([C:8]5[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][N:7]=5)[N:18]=[C:17]4[C:16]=3[CH:19]=2)(=[O:24])=[O:25])[CH2:45][CH2:44]1)([CH3:42])([CH3:41])[CH3:40]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 35305721-Tert-butylpiperazineHCID 86671459HCID 86671459, compound

Product 1

HCID 66558414HCID 66558414, compoundYield 22%

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 (0.34 mmol) in THF (10 mL) was added oxalyl chloride (143 μL, 1.69 mmol) and the resulting mixture stirred at RT for 10 min then cooled to 0° C. before DMF (126 μL, 1.69 mmol) was added. The resulting mixture was stirred for 3 h then azeotroped with toluene. The resulting residue was suspended in DCM (15 mL) and added to a solution of tert-butylpiperazine (96 mg, 0.68 mmol) and NEt3 (157 μL, 1.13 mmol) in DCM (10 mL) at RT The resulting mixture was stirred for 1 h then quenched with a saturated aqueous NaHCO3 solution. The organic phase was washed with H2O and brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 3-20% 2M NH3/MeOH in EtOAc then C18, gradient 25-45% MeOH in H2O). The resulting residue was partitioned between DCM and a saturated aqueous NaHCO3 solution, the organic phase dried (Na2SO4) and concentrated in vacuo affording 121 (25 mg, 22%). LCMS: RT 2.93 [M+H]+ 500.3. 1H NMR (DMSO, 400 MHz): δ 8.78 (1H, d, J=2.41 Hz), 8.00 (1H, s), 7.94 (1H, s), 7.62 (1H, dd, J=8.62, 2.42 Hz), 7.28 (1H, d, J=8.62 Hz), 5.74-5.74 (1H, m), 4.64-4.60 (4H, m), 2.92-2.85 (4H, m), 2.59-2.53 (4H, m), 1.49 (6H, d, J=6.62 Hz), 0.93 (9H, s)

Workup

  1. additionwas added
  2. stirringThe resulting mixture was stirred for 3 h
  3. customthen azeotroped with toluene
  4. stirringwas stirred for 1 h
  5. customthen quenched with a saturated aqueous NaHCO3 solution
  6. washThe organic phase was washed with H2O and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 3-20% 2M NH3/MeOH in EtOAc
  10. customThe resulting residue was partitioned between DCM
  11. dry with materiala saturated aqueous NaHCO3 solution, the organic phase dried (Na2SO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-91c5f35f6db946c7a4aa3a04657e8c86
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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