Triethylamine → HCID 68312738, compound

HRID 1530514Notes

Reaction equation

HRID 1530514 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[CH:21]([N:24]1[C:28]([C:29]2[N:38]=[C:37]3[N:31]([CH2:32][CH2:33][O:34][C:35]4[CH:42]=[CH:41][C:40]([S:43](Cl)(=[O:45])=[O:44])=[CH:39][C:36]=43)[CH:30]=2)=[N:27][CH:26]=[N:25]1)([CH3:23])[CH3:22]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:43]([C:40]2[CH:41]=[CH:42][C:35]3[O:34][CH2:33][CH2:32][N:31]4[C:37](=[N:38][C:29]([C:28]5[N:24]([CH:21]([CH3:22])[CH3:23])[N:25]=[CH:26][N:27]=5)=[CH:30]4)[C:36]=3[CH:39]=2)(=[O:45])=[O:44])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 86671461HCID 86671461, compound

Product 1

HCID 68312738HCID 68312738, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of piperazine-1-carboxylic acid tert-butyl ester (216 mg, 1.16 mmol) and NEt3 (272 μL, 1.93 mmol) in DCM (30 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 (270 mg, 0.39 mmol) in DCM (20 mL) and the resulting mixture warmed to RT after 10 min then stirred for 30 min. 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 0-5% MeOH in DCM) affording 4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfonyl]piperazine-1-carboxylic acid tert-butyl ester (196 mg, 93%) as a white solid. LCMS: RT 4.72 min [M+H]+ 544.3. 1H NMR (DMSO, 400 MHz): δ 8.77 (1H, d, J=2.43 Hz), 8.01 (1H, s), 7.94 (1H, d, J=0.61 Hz), 7.63 (1H, dd, J=8.64, 2.44 Hz), 7.28 (1H, d, J=8.64 Hz), 5.75-5.71 (1H, m), 4.67-4.57 (4H, m), 3.44-3.38 (4H, m), 2.91 (4H, t, J=4.83 Hz), 1.50 (6H, d, J=6.62 Hz), 1.32 (9H, s)

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 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-f8d861896f20411687f2581cd1904612
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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