Triethylamine → 1-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one

HRID 1777939Notes

Reaction equation

HRID 1777939 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:15][O:16][CH:17]([O:30][CH3:31])[C:18]1[C:27]([CH:28]=O)=[CH:26][C:25]2[CH2:24][CH2:23][CH2:22][NH:21][C:20]=2[N:19]=1.Cl.Cl.[NH2:34][CH2:35][CH2:36][N:37]([CH3:44])[CH2:38][C:39](OCC)=[O:40].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>ClCCCl>[CH3:15][O:16][CH:17]([O:30][CH3:31])[C:18]1[C:27]([CH2:28][N:34]2[CH2:35][CH2:36][N:37]([CH3:44])[CH2:38][C:39]2=[O:40])=[CH:26][C:25]2[CH2:24][CH2:23][CH2:22][NH:21][C:20]=2[N:19]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride3×HCID 22270088Ethyl 2-[2-aminoethyl(methyl)amino]acetate;dihydrochloride2×HCID 1180364262-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde2×

Product 1

HCID 1180366581-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (3.10 g, 14.61 mmol) was added to a mixture of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 2.30 g, 9.74 mmol), ethyl 2-((2-aminoethyl)(methyl)amino)acetate dihydrochloride (intermediate 82, 2.6 g, 14.61 mmol) and triethylamine (6.75 ml, 48.7 mmol) in 1,2-dichloroethane (20 ml) at room temperature. The reaction mixture was stirred for 21 h at room temperature and additional sodium triacetoxyborohydride (2.6 g, 9.74 mmol) was added. After a further 4 h stirring at room temperature, again additional sodium triacetoxyborohydride (1.3 g, 4.87 mmol) was added and the reaction maintained at 4° C. for 2.5 days. The reaction mixture was then warmed to room temperature, saturated aqueous NaHCO3 solution added, the mixture extracted with DCM (3×), the combined organic layers dried over Na2SO4 and evaporated. The residue was applied to a 120 g RediSep® silica column as a DCM solution and purified by normal phase chromatography, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as an orange foam. 1H NMR (400 MHz, CDCl3) δ 7.08 (s, 1H), 5.30 (s, br, 1H), 5.20 (s, 1H), 4.69 (s, 2H), 3.44-3.34 (m, 2H), 3.40 (s, 6H), 3.22-3.15 (m, 2H), 3.24 (s, 2H), 2.71-2.64 (m, 2H), 2.58-2.50 (m, 2H), 2.31 (s, 3H), 1.98-1.82 (m, 2H). (UPLC-MS 6) tR 0.33; ESI-MS 335.3 [M+H]+.

Workup

  1. stirringAfter a further 4 h stirring at room temperature
  2. temperaturethe reaction maintained at 4° C. for 2.5 days
  3. temperatureThe reaction mixture was then warmed to room temperature
  4. extractionthe mixture extracted with DCM (3×)
  5. dry with materialthe combined organic layers dried over Na2SO4
  6. customevaporated
  7. custompurified by normal phase chromatography
  8. washeluting with a gradient from DCM to 10% MeOH in DCM
  9. additionProduct containing fractions
  10. customevaporated

Sources & evidence

ORD record
ord-d595999578574a6e947e46f6bf9d9761
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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