Triethylamine → 6-({2-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)phenyl]ethylamino}methyl)-4H-benzo[1,4]thiazin-3-one

HRID 1435872Notes

Reaction equation

HRID 1435872 reaction equation
Cl.[CH3:2][O:3][C:4]1[N:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH2:22])=[CH:16][CH:15]=1.C(N(CC)CC)C.[O:30]=[C:31]1[NH:36][C:35]2[CH:37]=[C:38]([CH:41]=O)[CH:39]=[CH:40][C:34]=2[S:33][CH2:32]1.[BH4-].[Na+]>C(Cl)Cl.CCO>[CH3:2][O:3][C:4]1[N:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][CH2:41][C:38]2[CH:39]=[CH:40][C:34]3[S:33][CH2:32][C:31](=[O:30])[NH:36][C:35]=3[CH:37]=2)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 109433483-Oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carbaldehydeHCID 684436432-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)phenyl]ethylamine hydrochloride salt

Product 1

HCID 99119256-({2-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)phenyl]ethylamino}methyl)-4H-benzo[1,4]thiazin-3-oneYield 69%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)phenyl]ethylamine hydrochloride salt (1.76 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (10 mL) at RT was added triethylamine (0.74 mL, 5.28 mmole) and 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxaldehyde (0.34 g, 1.76 mmole). After 24 h, the reaction contents were concentrated and dried under high vacuum. To a stirred solution of the crude imine in dry EtOH (25 mL) at RT was added NaBH4 (0.66 g, 1.76 mmole). After 24 h, the reaction solution was concentrated under vacuum and to the residue was added 1M HCl (5 mL) and EtOAc (50 mL): After stirring for 1 h, 6M NaOH (1 mL) was added and the organic layer was separated, dried (Na2SO4) and concentrated. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (0.55 g, 69%) as light yellow solid: 1H NMR (400 MHz, CD3OD) δ 9.11 (d, J=4.5 Hz, 1H), 8.57 (d, J=9.1 Hz, 1H), 8.27 (d, J=4.5 Hz, 1H), 8.14 (m, 2H), 7.90 (s, 2H), 7.61 (m, 3H), 7.46 (d, J=7.1 Hz, 1H), 7.22 (m, 2H), 5.52 (m, 2H), 4.23 (s, 2H), 4.08 (s, 3H), 3.68 (s, 2H), 3.19 (m, 2H). LC-MS (ES) m/e 457 (M+H)+.

Workup

  1. customthe reaction contents
  2. concentrationwere concentrated
  3. customdried under high vacuum
  4. waitAfter 24 h
  5. concentrationthe reaction solution was concentrated under vacuum and to the residue
  6. additionwas added 1M HCl (5 mL) and EtOAc (50 mL)
  7. addition6M NaOH (1 mL) was added
  8. customthe organic layer was separated
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customPurification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH)

Sources & evidence

ORD record
ord-77aefa69b5164b918b8d9f5f8f4fff94
Source dataset
uspto-grants-2009_11
Patent number
US07618959B2

Reaction notes

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