Triethylamine → N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)methanesulfonamide

HRID 1778005Notes

Reaction equation

HRID 1778005 reaction equation
[CH3:1][O:2][CH:3]([O:21][CH3:22])[C:4]1[C:13]([CH2:14][NH:15][CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.CCN(CC)CC.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl>[CH3:22][O:21][CH:3]([O:2][CH3:1])[C:4]1[C:13]([CH2:14][N:15]([CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])[S:31]([CH3:30])(=[O:33])=[O:32])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 118036618N1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N2,N2-dimethylethane-1,2-diamine2×

Product 1

HCID 118036878N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N2,N2-dimethylethane-1,2-diamine (intermediate 199, 780 mg, 2.53 mmol) and NEt3 (0.705 mL, 5.06 mmol) in DCM (20 ml) at 0° C. was added dropwise methanesulfonyl chloride (0.215 ml, 2.78 mmol) and the solution was allowed to stir for 2 h at room temperature. The reaction mixture was quenched by the addition of NaHCO3 and diluted. Phases were separated and the water phase was extracted with DCM (2×), organic phases were combined, dried using Na2SO4, filtered and concentrated. The crude product was purified by reversed phase preparative HPLC eluting with a gradient of MeCN and water (RP 6, H2O/MeCN 95:05 to 40:60 in 25 min). Fractions containing the product were collected, diluted with water and basified with NaHCO3. The mixture was concentrated and extracted with DCM, dried using Na2SO4, filtered and dried to yield the title compound as a colorless waxy solid. (UPLC-MS 3) tR 0.34 min, ESI-MS 387.2 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 7.26 (s, 1H), 6.56-6.52 (m, 1H), 5.01 (s, 1H), 4.33 (s, 2H), 3.32 (s, 6H), 3.28-3.23 (m, 2H), 3.11 (t, 2H), 3.06 (s, 3H), 2.66 (t, 2H), 2.24 (t, 2H), 2.08 (s, 6H), 1.80-1.73 (m, 2H).

Workup

  1. customThe reaction mixture was quenched by the addition of NaHCO3
  2. additiondiluted
  3. customPhases were separated
  4. extractionthe water phase was extracted with DCM (2×), organic phases
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by reversed phase preparative HPLC
  9. washeluting with a gradient of MeCN and water (RP 6, H2O/MeCN 95:05 to 40:60 in 25 min)
  10. additionFractions containing the product
  11. customwere collected
  12. additiondiluted with water and basified with NaHCO3
  13. concentrationThe mixture was concentrated
  14. extractionextracted with DCM
  15. customdried
  16. filtrationfiltered
  17. customdried

Sources & evidence

ORD record
ord-c8d9221caee24ac99c85088236e64002
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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