Triethylamine → (R)-N-(1-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-(2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)ethyl)methanesulfonamide

HRID 1848546Notes

Reaction equation

HRID 1848546 reaction equation
[NH2:1][C@H:2]([C:22]1[C:23]([CH3:32])=[C:24]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:31])[O:26][CH2:25]2)[CH2:3][N:4]1[CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:6][CH2:5]1.C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>C(Cl)Cl>[CH3:32][C:23]1[C:22]([C@@H:2]([NH:1][S:41]([CH3:40])(=[O:43])=[O:42])[CH2:3][N:4]2[CH2:5][CH2:6][C:7]3([C:11](=[O:12])[N:10]([C:13]4[CH2:14][O:15][C:16](=[O:19])[C:17]=4[CH3:18])[CH2:9][CH2:8]3)[CH2:20][CH2:21]2)=[CH:30][CH:29]=[C:28]2[C:24]=1[CH2:25][O:26][C:27]2=[O:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 72948650(R)-8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 72948652(R)-N-(1-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-(2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)ethyl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (30 mg, 0.068 mmol) and triethylamine (29 μL, 0.20 mmol) in DCM (2 mL) was added methanesulfonyl chloride (5.3 μL, 0.068 mmol) at 0° C. under nitrogen atmosphere. The reaction mixture was allowed to warm to room temperature and stirred for 3 h. TLC indicated the reaction was complete. Evaporation of the solvent afforded the residue, which was taken up into small amount of DCM and purified by preparative TLC (dichloromethane: methanol=10:1) to give the title compound. 1H NMR (400 MHz, CDCl3): δ 7.63 (dd, J=8.0 Hz, J=8.8 Hz, 2H), 5.30 (s, 2H), 5.15 (s, 2H), 4.95-4.92 (m, 1H), 4.00 (t, J=7.2 Hz, 2H), 2.94-2.91 (m, 1H), 2.82-2.78 (m, 1H), 2.72 (s, 3H), 2.65-2.59 (m, 1H), 2.42-2.39 (m, 1H), 2.38-2.24 (m, 4H), 2.21-2.18 (m, 1H), 2.07 (t, J=7.2 Hz, 2H), 1.92 (s, 3H), 1.86-1.72 (m, 2H), 1.52-1.47 (m, 2H). MS-ESI (m/z): 518 (M+1)+.

Workup

  1. customEvaporation of the solvent
  2. customafforded the residue, which
  3. custompurified by preparative TLC (dichloromethane: methanol=10:1)

Sources & evidence

ORD record
ord-abc4d26ac7384be5bb57058c3ad5e721
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

Loading…