Triethylamine → 2-(Trimethylsilyl)ethyl 4-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-3-oxopiperazine-1-carboxylate

HRID 1777974Notes

Reaction equation

HRID 1777974 reaction equation
[CH3:1][O:2][CH:3]([O:16][CH3:17])[C:4]1[C:13]([CH:14]=O)=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:29][CH2:30][CH2:31][N:32]([C:39]([O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])=[O:40])[CH2:33][C:34](OCC)=[O:35].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][O:2][CH:3]([O:16][CH3:17])[C:4]1[C:13]([CH2:14][N:29]2[CH2:30][CH2:31][N:32]([C:39]([O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])=[O:40])[CH2:33][C:34]2=[O:35])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 1180364262-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde2×HCID 131734791Ethyl 2-((2-aminoethyl)((2-(trimethylsilyl)ethoxy)carbonyl)amino)acetate para-toluene sulphonate2×

Product 1

HCID 1317347902-(Trimethylsilyl)ethyl 4-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-3-oxopiperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 2.50 g, 10.58 mmol), ethyl 2-((2-aminoethyl)((2-(trimethylsilyl)ethoxy)carbonyl)amino)acetate para-toluene sulphonate (intermediate 124, 8.37 g, 18.09 mmol) and triethylamine (3.23 ml, 23.28 mmol) in 1,2-dichloroethane (10 ml) at room temperature was stirred for 12 h and sodium triacetoxyborohydride (4.72 g, 21.16 mmol) added. The reaction mixture was stirred for 18 h at room temperature, partitioned between saturated aqueous NaHCO3 solution and EtOAc, the EtOAc phase washed with brine, dried over MgSO4 and evaporated. The residue was applied to a RediSep® silica column and purified by normal phase chromatography, eluting with a gradient from heptane to EtOAc. Product containing fractions were combined and evaporated to give the title compound as a yellow oil. (UPLC-MS 6) tR 0.42; ESI-MS 322.2 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred for 18 h at room temperature
  2. custompartitioned between saturated aqueous NaHCO3 solution and EtOAc
  3. washthe EtOAc phase washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. custompurified by normal phase chromatography
  7. washeluting with a gradient from heptane to EtOAc
  8. additionProduct containing fractions
  9. customevaporated

Sources & evidence

ORD record
ord-7ba82568d55a4b93a20d3705c4eff039
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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