Triethylamine → HCID 54692325, compound

HRID 1162852Notes

Reaction equation

HRID 1162852 reaction equation
C([O:4][C:5]1[C:10](=[O:11])[N:9]([CH:12]([CH3:14])[CH3:13])[C:8](=[O:15])[N:7]2[CH:16]([CH2:29][CH2:30][NH:31][CH3:32])[CH2:17][N:18]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:19](=[O:20])[C:6]=12)(=O)C.[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)CC)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][N:18]2[CH2:17][CH:16]([CH2:29][CH2:30][N:31]([CH3:32])[S:34]([CH3:33])(=[O:36])=[O:35])[N:7]3[C:8](=[O:15])[N:9]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:11])[C:5]([OH:4])=[C:6]3[C:19]2=[O:20])=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68432475HCID 68432475, compound

Product 1

HCID 54692325HCID 54692325, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(4-Fluorobenzyl)-7-isopropyl-4-[2-(methylamino)ethyl]-1,6,8-trioxo-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidin-9-yl acetate (Example 67, Step 2, 37 mg, 0.08 mmol) in CH2Cl2 (1.5 mL) was treated with a large excess of reagents (70 μL MsCl, 270 μL triethylamine and 20 mg DMAP). Stirring the reaction at ambient temperature over night gave complete conversion to the sulfonamide with exchange of the 9-acetate to the 9-mesylate. The solvent was removed under a steady nitrogen stream at 50° C. and the residue dissolved in MeOH (1 mL) and treated with a solution of sodium methoxide in MeOH (25 wt %, 2.5 mL). After four days of stirring at ambient temperature, cleavage of the 9-mesylate to the 9-hydroxy was complete. The mixture was quenched by the addition of TFA and water and was then concentrated under a steady stream of nitrogen at 50° C. The crude material was purified by reverse phase preparative HPLC to afford the title compound as an off-white solid. 1H NMR (500 MHz, CDCl3) δ 11.73 (s, 1 H), 7.38-7.27 (m, 2 H), 7.09-7.05 (m, 2 H), 5.22-5.15 (m, 1 H), 4.96 (d, J=14.5 Hz, 1 H), 4.78-4.76 (m, 1 H), 4.37 (d, J=14.0 Hz, 1 H), 3.72 (dd, J=1.5, 14.0 Hz, 1 H), 3.62 (dd, J=3.8, 14.0 Hz, 1 H), 2.83 (s, 3 H), 2.80-2.66 (m, 5 H), 1.90-1.83 (m, 1 H), 1.56-1.49 (m, 1 H), 1.47 (d, J=7.0 Hz, 6 H). HRMS (APCI) M+H: calcd for (C21H28FN4O6S)+ 483.1708. found 483.1729.

Workup

  1. customthe reaction at ambient temperature over night

Sources & evidence

ORD record
ord-829e57bef9e94c59a3470bf5eb37aa7a
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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