Triethylamine → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-(4-isopropylpiperazin-1-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530509Notes

Reaction equation

HRID 1530509 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].CCN(CC)CC.[CH:17]([N:20]1[C:24]([C:25]2[N:34]=[C:33]3[N:27]([CH2:28][CH2:29][O:30][C:31]4[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][C:32]=43)[CH:26]=2)=[N:23][CH:22]=[N:21]1)([CH3:19])[CH3:18]>C(Cl)Cl>[CH:17]([N:20]1[C:24]([C:25]2[N:34]=[C:33]3[C:32]4[CH:35]=[C:36]([S:39]([N:7]5[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]5)(=[O:41])=[O:40])[CH:37]=[CH:38][C:31]=4[O:30][CH2:29][CH2:28][N:27]3[CH:26]=2)=[N:23][CH:22]=[N:21]1)([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 780131-IsopropylpiperazineHCID 86671461HCID 86671461, compound

Product 1

HCID 683132372-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-(4-isopropylpiperazin-1-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 1-isopropylpiperazine (50 mg, 0.39 mmol) and NEt3 (90 μL, 0.65 mmol) in DCM (8 mL) at 0° C. was added a suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfonyl chloride from Example 121 (0.13 mmol) in DCM (8 mL) and the resulting mixture warmed to RT after 10 min then stirred for 2 h. The reaction mixture was diluted with DCM, washed with a saturated aqueous NaHCO3 solution then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-7% 2M NH3/MeOH in DCM) affording 128 (41 mg, 65%) as a white solid. LCMS: RT 2.90 min [M+H]+ 486.3. 1H NMR (DMSO, 400 MHz): δ 8.79 (1H, d, J=2.41 Hz), 8.00 (1H, s), 7.94 (1H, d, J=0.61 Hz), 7.63 (1H, dd, J=8.62, 2.43 Hz), 7.28 (1H, d, J=8.62 Hz), 5.76-5.69 (1H, m), 4.64-4.62 (4H, m), 2.94-2.87 (4H, m), 2.62-2.61 (1H, m), 2.54-2.43 (4H, m), 1.49 (6H, d, J=6.62 Hz), 0.89 (6H, d, J=6.53 Hz)

Workup

  1. washwashed with a saturated aqueous NaHCO3 solution
  2. dry with materialthen dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-7% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-8a57bf20c7f541148ce45b05a4ab17e8
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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