Water → N-Isopropyl-2-{3-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-acetamide

HRID 1190739Notes

Reaction equation

HRID 1190739 reaction equation
Cl[CH2:2][C:3]([NH:5][CH:6]([CH3:8])[CH3:7])=[O:4].[NH:9]1[CH2:12][CH:11]([C:13]2[CH:35]=[CH:34][C:16]3[C:17]4[N:18]=[C:19]([C:25]5[N:26]([CH:31]([CH3:33])[CH3:32])[N:27]=[C:28]([CH3:30])[N:29]=5)[S:20][C:21]=4[CH2:22][CH2:23][O:24][C:15]=3[CH:14]=2)[CH2:10]1.C(N(CC)CC)C.O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH:6]([NH:5][C:3](=[O:4])[CH2:2][N:9]1[CH2:12][CH:11]([C:13]2[CH:35]=[CH:34][C:16]3[C:17]4[N:18]=[C:19]([C:25]5[N:26]([CH:31]([CH3:33])[CH3:32])[N:27]=[C:28]([CH3:30])[N:29]=5)[S:20][C:21]=4[CH2:22][CH2:23][O:24][C:15]=3[CH:14]=2)[CH2:10]1)([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 761712-chloro-N-(1-methylethyl)acetamideHCID 582041048-Azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 67050515N-Isopropyl-2-{3-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-acetamideYield 11.6%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

2-Chloro-N-isopropylacetamide (0.124 g, 0.917 mmol) and tetra-n-butylammonium iodide (0.678 g, 0.00183 mol) were premixed in methylene chloride (3 mL). This solution was added dropwise to a solution of 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene from Example 519 (0.350 g, 0.917 mmol) and triethylamine (0.256 mL, 0.00183 mol) in methylene chloride (7 mL). The reaction was stirred at room temperature for 24 hours. Water was added and the mixture was extracted 3 times with methylene chloride. The organic layers were combined, dried with MgSO4 and concentrated. The crude was purified by reverse-phase HPLC to obtain 527 as a white solid (51 mg). MS (ESI+) 481.2. 1H NMR (400 MHz, DMSO) δ 8.29 (d, J=8.2 Hz, 1H), 7.42 (d, J=7.9 Hz, 1H), 7.20 (dd, J=8.3, 1.6 Hz, 1H), 7.03 (d, J=1.5 Hz, 1H), 5.87-5.65 (m, 1H), 4.36 (t, J=5.0 Hz, 2H), 3.87 (dq, J=13.2, 6.6 Hz, 1H), 3.76-3.59 (m, 3H), 3.42 (t, J=5.0 Hz, 2H), 3.22 (t, J=6.0 Hz, 2H), 3.04 (s, 2H), 2.32 (s, 3H), 1.52 (d, J=6.6 Hz, 6H), 1.07 (d, J=6.6 Hz, 6H)

Workup

  1. extractionthe mixture was extracted 3 times with methylene chloride
  2. dry with materialdried with MgSO4
  3. concentrationconcentrated
  4. customThe crude was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-24c93e2cac3c4ef8bef15c72c3fdd22a
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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