Sodium Sulfate → 6-({[((3S)-1-{2-[3-chloro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 639073Notes

Reaction equation

HRID 639073 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][C@@H:16]([CH2:19][NH2:20])[CH2:15]1)=[N:9][C:8]([O:21][CH3:22])=[CH:7][CH:6]=2.[O:23]=[C:24]1[CH2:29][S:28][C:27]2[CH:30]=[CH:31][C:32]([CH:34]=O)=[N:33][C:26]=2[NH:25]1.[O-]S([O-])(=O)=O.[Na+].[Na+].C([O-])(O)=O.[Na+].[BH4-].[Na+]>C(Cl)Cl.CCO>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][C@@H:16]([CH2:19][NH:20][CH2:34][C:32]3[CH:31]=[CH:30][C:27]4[S:28][CH2:29][C:24](=[O:23])[NH:25][C:26]=4[N:33]=3)[CH2:15]1)=[N:9][C:8]([O:21][CH3:22])=[CH:7][CH:6]=2

Participants

8

Reactant 5

HCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 59026202HCID 59026202, compound

Product 1

HCID 116847356-({[((3S)-1-{2-[3-chloro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 9.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [((3S)-1-{2-[3-Chloro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]amine (100 mg, 0.31 mmol) in dry CH2Cl2 (5 mL) and dry EtOH (5 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (67 mg, 0.34 mmol) along with a small amount of Na2SO4 and NaHCO3. After 24 h at RT, NaBH4 (12 mg, 0.32 mmol) was added. After 2 h, silica gel (5 g) was added to the reaction solution and the suspension was concentrated under vacuum to a dry solid. Purification on silica gel afforded the title compound as a light yellow solid (15 mg, 9.4%): LC/MS (ES) m/e 499/501 (M+H)+; 1H NMR (CD3OD, 400 MHz) δ 8.78 (s, 1H), 8.25 (d, J=9.1 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.28 (d, J=9.1 Hz, 1H), 7.12 (d, J=7.8 Hz, 1H), 4.35 (s, 2H), 4.1 (s, 3H), 3.9 (m, 4H), 3.66 (s, 4H), 3.5 (m, 4H), 3.3 (m, 2H), 2.9-3.0 (m, 1H), 2.2-2.3 (m, 1H), 1.95-2.05 (m, 1H).

Workup

  1. waitAfter 2 h
  2. additionsilica gel (5 g) was added to the reaction solution
  3. concentrationthe suspension was concentrated under vacuum to a dry solid
  4. customPurification on silica gel

Sources & evidence

ORD record
ord-93d2529af2034c8eb5ca273bbd9c325c
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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