Triethylamine → N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-3-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777988Notes

Reaction equation

HRID 1777988 reaction equation
CS(O[CH2:6][C:7]1[C:8]([CH:33]([O:36][CH3:37])[O:34][CH3:35])=[N:9][C:10]2[N:11]([C:17](=[O:32])[NH:18][C:19]3[CH:24]=[C:23]([NH:25][CH2:26][CH2:27][O:28][CH3:29])[C:22]([C:30]#[N:31])=[CH:21][N:20]=3)[CH2:12][CH2:13][CH2:14][C:15]=2[CH:16]=1)(=O)=O.CCN(CC)CC.[CH3:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][C:47]1=[O:52]>C(Cl)Cl>[C:30]([C:22]1[C:23]([NH:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:24][C:19]([NH:18][C:17]([N:11]2[C:10]3[C:15](=[CH:16][C:7]([CH2:6][N:49]4[CH2:50][CH2:51][N:46]([CH3:45])[C:47](=[O:52])[CH2:48]4)=[C:8]([CH:33]([O:36][CH3:37])[O:34][CH3:35])[N:9]=3)[CH2:14][CH2:13][CH2:12]2)=[O:32])=[N:20][CH:21]=1)#[N:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 43990421-Methylpiperazin-2-oneHCID 118036268(8-((5-Cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate2×

Product 1

HCID 118036296N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-3-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (8-((5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate (intermediate 170, 368 mg, 0.657 mmol) in DCM (2.7 ml) at room temperature was added NEt3 (0.319 ml, 2.301 mmol) followed by 1-methylpiperazin-2-one (120 mg, 1.052 mmol). The reaction mixture was stirred at room temperature for 2 h and partitioned between DCM and water. The water layer was extracted multiple times with DCM, the combined organic layers were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography using a gradient of MeOH (0-3%) in DCM to yield the title compound as a white solid. (UPLC-MS 3) tR 0.87 min; ESI-MS 553.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 13.75 (s, 1H), 8.20 (s, 1H), 7.64 (br s, 1H), 7.58 (s, 1H), 5.56 (s, 1H), 5.23 (d, 1H), 4.06-4.01 (m, 2H), 3.70 (br s, 2H), 3.63 (t, 2H), 3.50-3.42 (m, 8H), 3.40 (s, 3H), 3.31 (br s, 2H), 3.14 (br s, 2H), 2.96 (br s, 3H), 2.87-2.80 (m, 2H), 2.71 (br s, 2H), 2.03-1.96 (m, 2H).

Workup

  1. custompartitioned between DCM and water
  2. extractionThe water layer was extracted multiple times with DCM
  3. customthe combined organic layers were dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-4f9f9ff48e044848b7b52b891ad290a2
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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