Acetic Acid → {2-[5-(1-Methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-3,4-dihydro-2H-[1,7]naphthyridin-1-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 530351Notes

Reaction equation

HRID 530351 reaction equation
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:21]=[N:20][CH:19]=[C:18]4[C:13]=3[CH2:14][CH2:15][CH2:16][NH:17]4)=[CH:9][CH:10]=2)[CH2:5][CH2:4][C:3]1=[O:22].O=[CH:24][CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.C(Cl)Cl.C1COCC1>[C:29]([O:28][C:27](=[O:33])[NH:26][CH2:25][CH2:24][N:17]1[C:18]2[C:13](=[C:12]([C:8]3[CH:7]=[C:6]4[C:11](=[CH:10][CH:9]=3)[N:2]([CH3:1])[C:3](=[O:22])[CH2:4][CH2:5]4)[CH:21]=[N:20][CH:19]=2)[CH2:14][CH2:15][CH2:16]1)([CH3:32])([CH3:31])[CH3:30]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 866799281-Methyl-6-(1,2,3,4-tetrahydro-1,7-naphthyridin-5-yl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 71536484{2-[5-(1-Methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-3,4-dihydro-2H-[1,7]naphthyridin-1-yl]-ethyl}-carbamic acid tert-butyl esterYield 24.2%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-methyl-6-(1,2,3,4-tetrahydro-1,7-naphthyridin-5-yl)-3,4-dihydroquinolin-2(1H)-one (intermediate A-5, 0.1 g, 0.341 mmol) in DCE (3 mL)/THF (1.5 mL) were added tert-butyl 2-oxoethylcarbamate (0.081 g, 0.511 mmol), acetic acid (0.02 g, 0.341 mmol) and the reaction mixture was stirred at room temperature for 10 min. Then, sodium triacetoxyborohydride (0.144 g, 0.682 mmol) was added and stirring was continued at room temperature over night. Then, the mixture was diluted with DCM, poured into aq NaHCO3 and extracted with DCM (2×25 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by reverse phase HPLC on a Gemini-NX column, eluting with a 20 to 98% MeOH—H2O (0.05% TEA) gradient to give the title compound (0.036 g, 24%) as a white foam. MS: 437.2 (M+H+).

Workup

  1. stirringstirring
  2. waitwas continued at room temperature over night
  3. extractionextracted with DCM (2×25 mL)
  4. washCombined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by reverse phase HPLC on a Gemini-NX column
  9. washeluting with a 20 to 98% MeOH—H2O (0.05% TEA) gradient

Sources & evidence

ORD record
ord-46c75fa127ee4202ba645e255413c4dd
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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