Triacetoxyborohydride → 1-{2-[4-({[5-chloro-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

HRID 1881736Notes

Reaction equation

HRID 1881736 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:32]=O)[CH:27]=[N:28][C:29]=1[CH2:30][OH:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>ClCCl.CO>[Cl:23][C:24]1[CH:25]=[C:26]([CH2:32][NH:1][CH:2]2[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]3[C:19]4[C:14](=[N:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[CH:13]=[CH:12][C:11]3=[O:22])[CH2:6][CH2:7]2)[CH:27]=[N:28][C:29]=1[CH2:30][OH:31]

Participants

7

Reactant 4

HCID 2724942TriacetoxyborohydrideHCID 5049666Sodium triacetoxyborohydride3×HCID 578151881-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one2×HCID 580017855-Chloro-6-(hydroxymethyl)-3-pyridinecarbaldehyde2×

Product 1

HCID 468464901-{2-[4-({[5-chloro-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-oneYield 29.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one (Intermediate 29: 100 mg, 0.331 mmol) was dissolved in a mixture of Dichloromethane (DCM) (4 mL) and Methanol (0.444 mL). Aldehyde 5-chloro-6-(hydroxymethyl)-3-pyridinecarbaldehyde (Intermediate 39: 56.7 mg, 0.331 mmol) was added and the mixture was left at room temp. for 3 hours. Then sodium triacetoxy borohydride (210 mg, 0.992 mmol) was added and after 2 hours 2 more eq. of triacetoxy borohydride were added leaving the reaction under stirring overnight. LCMS overnight showed still imine remaining so 3 eq more of sodium triacetoxy borohydride were added and 2 eq more after 3 hours leaving the reaction overnight. Next morning 2 more eq. of sodium triacetoxy borohydride were added and after 3H reaction was stopped. Volatiles were removed under vacuum and the corresponding crude was diluted with DCM and washed with NaHCO3 several times. Organic layers were dried over Na2SO4, filtered and volatiles removed under vacuum. Corresponding crude was purified by flash master chromatography. Si II, 5 g. DCM/MeOH (0-30%), to obtain a solid which was left in the oven overnight to afford 45 mg of the final compound as a pale yellow solid.

Workup

  1. additionwere added
  2. customleaving
  3. customthe reaction
  4. customLCMS overnight
  5. additionwere added
  6. custom2 eq more after 3 hours leaving
  7. customthe reaction overnight
  8. customafter 3H reaction
  9. customVolatiles were removed under vacuum
  10. additionthe corresponding crude was diluted with DCM
  11. washwashed with NaHCO3 several times
  12. dry with materialOrganic layers were dried over Na2SO4
  13. filtrationfiltered
  14. customvolatiles removed under vacuum
  15. customwas purified by flash master chromatography
  16. customDCM/MeOH (0-30%), to obtain a solid which
  17. waitwas left in the oven overnight

Sources & evidence

ORD record
ord-af73716ebbbd4cbe856d1c1d97e9c529
Source dataset
uspto-grants-2012_11
Patent number
US08318940B2

Reaction notes

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