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Tetrahydrofuran → (racemic) 7-(dimethoxymethyl)-N-(5-(1-hydroxypentyl)pyridin-2-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777864
Notes
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Reaction equation

HRID 1777864 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:8]([C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#N)=[CH:22][N:21]=1)=[O:18])[CH2:7][CH2:6][CH2:5]2.[Li][CH2:29][CH2:30][CH2:31][CH3:32].[BH4-].[Na+].C1C[O:38]CC1>C(Cl)Cl>[CH3:14][O:13][CH:12]([O:15][CH3:16])[C:11]1[N:10]=[C:9]2[C:4]([CH2:5][CH2:6][CH2:7][N:8]2[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]([OH:38])[CH2:29][CH2:30][CH2:31][CH3:32])=[CH:22][N:21]=2)=[O:18])=[CH:3][CH:2]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 1180363436-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×HCID 178418339Butyllithium

Product 1

HCID 118036262(racemic) 7-(dimethoxymethyl)-N-(5-(1-hydroxypentyl)pyridin-2-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2H, 50 mg, 0.116 mmol) in THF (2 ml) at −78° C. was treated with n-BuLi (1.5 M in hexane, 217 μl, 0.326 mmol) and stirred for 2 min. The reaction mixture was treated with N,N-dimethylform-13C-amide (45.6 μl, 0.578 mmol) and stirred for 0.5 h. The reaction was quenched by addition of sat. aq. NH4Cl, warmed to room temperature and extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in MeOH (2 ml) and DCM (1 ml), treated with NaBH4 (8.75 mg, 0.231 mmol) and stirred for 10 min. The reaction was quenched by addition of sat. aq. NH4Cl and extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) the product containing fractions were concentrated to give the title compound as a yellow oil. (UPLC-MS 3) tR 1.09 min; ESI-MS 415.2 [M+H]+.

Workup

  1. additionThe reaction mixture was treated with N,N-dimethylform-13C-amide (45.6 μl, 0.578 mmol)
  2. stirringstirred for 0.5 h
  3. customThe reaction was quenched by addition of sat. aq. NH4Cl
  4. extractionextracted with EtOAc (2×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeOH (2 ml)
  9. stirringstirred for 10 min
  10. customThe reaction was quenched by addition of sat. aq. NH4Cl
  11. extractionextracted with EtOAc (2×)
  12. dry with materialThe combined organic layers were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) the product
  16. additioncontaining fractions
  17. concentrationwere concentrated

Sources & evidence

ORD record
ord-56f3dfcb53914612a18740a56faa5841
Source dataset
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09266883B2

Reaction notes

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