Triethylamine → HCID 57904952, compound

HRID 1093125Notes

Reaction equation

HRID 1093125 reaction equation
[NH2:1][C:2]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][N:4]1[C:11](=[O:27])[C:12]([OH:26])=[C:13]([C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[O:16])[N:14]=[C:3]21.CCN(CC)CC.[CH3:35][N:36]([CH3:41])[S:37](Cl)(=[O:39])=[O:38].[O-]CC.[Na+]>C(Cl)Cl.CO>[CH3:35][N:36]([CH3:41])[S:37]([NH:1][C:2]12[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10]1)[CH2:5][N:4]1[C:11](=[O:27])[C:12]([OH:26])=[C:13]([C:15]([NH:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)=[O:16])[N:14]=[C:3]21)(=[O:39])=[O:38]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 83372Dimethylsulphamoyl chlorideHCID 2723922Sodium ethoxideHCID 5790475010-Amino-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

Product 1

HCID 57904952HCID 57904952, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 10-amino-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (25 mg, 0.067 mmol) in CH2Cl2 (2 mL) was added Et3N (0.047 mL, 0.336 mmol) followed by dimethylsulfamoyl chloride (0.036 mL, 0.336 mmol) and the resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated to give crude product which was dissolved in methanol (2 mL) and treated with sodium ethoxide (0.2 ml, 21 wt % in ethanol) and the heated at 70° C. overnight. The mixture was then cooled, concentrated and purified by preparative HPLC to afford the title compound as a white solid (3.5 mg, 11% yield). 1H NMR (500 MHz, CDCl3) δ: 12.00 (s, 1H), 8.90 (s, 1H), 7.34 (dd, 2H, J=8.39 & 5.34 Hz), 7.01 (t, 2H, J=8.55 Hz), 4.53 (d, 2H, J=6.41 Hz), 4.15 (d, 2H, J=3.97 Hz), 2.77 (s, 6H), 2.50 (s, 1H), 2.12 (t, 4H, J=7.63 Hz), 1.85-1.97 (m, 2H), 1.64-1.73 (m, 2H). LCMS (M+H)=480.21. HPLC purity: >95%.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give crude product which
  3. temperaturethe heated at 70° C. overnight
  4. temperatureThe mixture was then cooled
  5. concentrationconcentrated
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-0616eb41cf6e4fe6811258274d2cd459
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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