Triethylamine → 6-((4-acetylpiperazin-1-yl)methyl)-N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777991Notes

Reaction equation

HRID 1777991 reaction equation
CS(O[CH2:6][C:7]1[C:8]([CH:32]([O:35][CH3:36])[O:33][CH3:34])=[N:9][C:10]2[N:11]([C:17](=[O:31])[NH:18][C:19]3[CH:24]=[C:23]([O:25][CH:26]([CH3:28])[CH3:27])[C:22]([C:29]#[N:30])=[CH:21][N:20]=3)[CH2:12][CH2:13][CH2:14][C:15]=2[CH:16]=1)(=O)=O.C(N(CC)CC)C.[C:44]([N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1)(=[O:46])[CH3:45]>C(Cl)Cl.O>[C:44]([N:47]1[CH2:52][CH2:51][N:50]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10](=[N:9][C:8]=2[CH:32]([O:33][CH3:34])[O:35][CH3:36])[N:11]([C:17]([NH:18][C:19]2[CH:24]=[C:23]([O:25][CH:26]([CH3:28])[CH3:27])[C:22]([C:29]#[N:30])=[CH:21][N:20]=2)=[O:31])[CH2:12][CH2:13][CH2:14]3)[CH2:49][CH2:48]1)(=[O:46])[CH3:45]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 837951-AcetylpiperazineHCID 118036581(8-((5-Cyano-4-isopropoxypyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate2×

Product 1

HCID 1180368666-((4-acetylpiperazin-1-yl)methyl)-N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (8-((5-cyano-4-isopropoxypyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate (intermediate 167, 188 mg, 0.362 mmol) in DCM (1 ml) was added triethylamine (0.176 mL, 1.267 mmol) followed by 1-acetylpiperazine (71.0 mg, 0.543 mmol) and the reaction mixture was stirred at room temperature for approximately 2 h. The reaction mixture was diluted with DCM and water and extracted. The water phase was extracted with DCM (2×), the combined organic layers were dried using Na2SO4, filtered and concentrated. The crude product was purified via silica gel column chromatography, eluting with a gradient of MeOH (1-5%) in DCM. Product fractions were combined and concentrated to yield the title compound as a white solid. (UPLC-MS 3) tR 0.97 min, ESI-MS 552.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 14.01 (s, 1H), 8.38 (s, 1H), 7.96 (s, 1H), 7.62 (s, 1H), 5.68 (s, 1H), 4.88-4.80 (m, 1H), 4.07-4.02 (m, 2H), 3.66-3.58 (m, 4H), 3.47-3.42 (m, 8H), 2.86 (t, 2H), 2.45 (t, 2H), 2.41 (t, 2H), 2.09 (s, 3H), 2.04-1.96 (m, 2H), 1.44 (d, 6H).

Workup

  1. extractionextracted
  2. extractionThe water phase was extracted with DCM (2×)
  3. customthe combined organic layers were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified via silica gel column chromatography
  7. washeluting with a gradient of MeOH (1-5%) in DCM
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-48ccc54fa30b48539af02ca600e5af02
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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