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

HRID 1778005ノート

反応式

HRID 1778005 の反応式
[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

参加物

5

反応物 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 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c8d9221caee24ac99c85088236e64002
出典データセット
uspto-grants-2016_02
特許番号
US09266883B2

反応ノート

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