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

HRID 1778002Notes

Reaction equation

HRID 1778002 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.[C:30](Cl)(=[O:32])[CH3:31]>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])[C:30](=[O:32])[CH3:31])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 118036618N1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N2,N2-dimethylethane-1,2-diamine2×

Product 1

HCID 118036906N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)acetamide

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, 300 mg, 0.973 mmol) and NEt3 (0.270 mL, 1.937 mmol) in DCM (10 ml) was added acetyl chloride (0.075 mL, 1.055 mmol) at room temperature and the reaction mixture was stirred for approximately 10 min. The reaction mixture was quenched with saturated aqueous NaHCO3 and diluted with DCM. Phases were separated and the water phase was extracted with DCM (2×), organic phases were combined, dried using Na2SO4, filtered and concentrated to yield the title compound, which was directly used in the next step without further purification. (UPLC-MS 3) tR 0.30 min, ESI-MS 351.2 [M+H]+. 1H NMR (600 MHz, DMSO-d6) (indicates an overlapping mixture of rotamers of the title compound in an approximate mixture of 0.5:0.5) δ 6.94 (s, 0.5H), 6.92 (s, 0.5H), 6.52-6.48 (m, 0.5H), 6.48-6.43 (m, 0.5H), 4.98 (s, 0.5H), 4.96 (s, 0.5H), 4.53 (s, 2H), 3.32 (s, 3H), 3.31 (s, 3H), 3.28-3.22 (m, 3H), 3.19 (t, 1H), 2.65 (t, 1H), 2.61 (t, 1H), 2.31 (t, 1H), 2.26 (t, 1H), 2.15-2.06 (m, 7.5H), 1.97 (s, 1.5H), 1.79-1.71 (m, 2H).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. additiondiluted with DCM
  3. customPhases were separated
  4. extractionthe water phase was extracted with DCM (2×), organic phases
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-40bd1b47e67e4ddd9ed8b12e923bfa97
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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