2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde → N-(5-cyano-4-ethyl pyridin-2-yl)-7-(dimethoxymethyl)-6-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777966Notes

Reaction equation

HRID 1777966 reaction equation
[CH3:1][O:2][CH:3]([O:16][CH3:17])[C:4]1[C:13]([CH:14]=[O:15])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.C1([O:24][C:25](=O)[NH:26][C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[C:30]([C:35]#[N:36])=[CH:29][N:28]=2)C=CC=CC=1>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:35]([C:30]1[C:31]([CH2:33][CH3:34])=[CH:32][C:27]([NH:26][C:25]([N:7]2[C:6]3[C:11](=[CH:12][C:13]([CH:14]=[O:15])=[C:4]([CH:3]([O:2][CH3:1])[O:16][CH3:17])[N:5]=3)[CH2:10][CH2:9][CH2:8]2)=[O:24])=[N:28][CH:29]=1)#[N:36]

Participants

5

Reactant 2

HCID 1180364262-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde2×HCID 125470423Phenyl(5-cyano-4-ethylpyridin-2-yl)carbamate2×

Product 1

HCID 118036273N-(5-cyano-4-ethyl pyridin-2-yl)-7-(dimethoxymethyl)-6-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 400 mg, 1.69 mmol), phenyl(5-cyano-4-ethylpyridin-2-yl)carbamate (intermediate 111, 773 mg, 2.89 mmol) and DMAP (293 mg, 2.40 mmol) in DMF (3 ml) was heated for 1 h at 90° C. The cooled reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution, extracted 2× with EtOAc, the organic layers dried over Na2SO4 and evaporated. The residue was applied to a 40 g RediSep® column and purified by normal phase chromatography, eluting with hetane and then a gradient from heptane to EtOAc. Product containing fractions were combined and evaporated to give the title compound. (UPLC-MS 6) tR 1.23; ESI-MS 410.3 [M+H]+.

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between EtOAc and saturated aqueous NaHCO3 solution
  3. extractionextracted 2× with EtOAc
  4. dry with materialthe organic layers dried over Na2SO4
  5. customevaporated
  6. custompurified by normal phase chromatography
  7. washeluting with hetane
  8. additionProduct containing fractions
  9. customevaporated

Sources & evidence

ORD record
ord-62e0d95e688d4270ae5f67b8c305190e
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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