Dichloromethane → 3-{[({(3S,4S)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-4-hydroxy-3-pyrrolidinyl}methyl)amino]methyl}-5H-pyridazino[3,4-b][1,4]thiazin-6(7H)-one

HRID 657028Notes

Reaction equation

HRID 657028 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@H:7]([OH:8])[CH2:6][N:5]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([F:21])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:22])[CH2:4]1.[O:23]=[C:24]1[CH2:29][S:28][C:27]2[N:30]=[N:31][C:32]([CH:34]=O)=[CH:33][C:26]=2[NH:25]1.C(Cl)Cl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[F:21][C:18]1[CH:19]=[C:20]2[C:15]([CH:14]=[CH:13][C:12](=[O:22])[N:11]2[CH2:10][CH2:9][N:5]2[CH2:6][C@@H:7]([OH:8])[C@@H:3]([CH2:2][NH:1][CH2:34][C:32]3[N:31]=[N:30][C:27]4[S:28][CH2:29][C:24](=[O:23])[NH:25][C:26]=4[CH:33]=3)[CH2:4]2)=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 218736976-oxo-6,7-dihydro-5H-pyridazino[3,4-b][1,4]thiazine-3-carbaldehydeHCID 689912461-{2-[(3S,4S)-3-(aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-fluoro-2(1H)-quinolinone

Product 1

HCID 250311503-{[({(3S,4S)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-4-hydroxy-3-pyrrolidinyl}methyl)amino]methyl}-5H-pyridazino[3,4-b][1,4]thiazin-6(7H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-{2-[(3S,4S)-3-(aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-fluoro-2(1H)-quinolinone (100 mg; 0.33 mmol) and 6-oxo-6,7-dihydro-5H-pyridazino[3,4-b][1,4]thiazine-3-carbaldehyde (for a synthesis see WO2004058144, Example 58) (65 mg, 0.33 mmol) in methanol (2 mL), DCM (4 mL) was stirred at room temperature overnight. Sodium triacetoxyborohydride (210 mg; 1.0 mmol) was added and the mixture was stirred at room temperature for 4 h. The reaction was evaporated and chromatographed on silica gel, eluting with 0-10% methanol-DCM-1% NH4OH to give 42 mg of the title compound as an oil which solidified to an off-white powder upon standing.

Workup

  1. customThe reaction was evaporated
  2. customchromatographed on silica gel
  3. washeluting with 0-10% methanol-DCM-1% NH4OH

Sources & evidence

ORD record
ord-9dc4e68281a34aa69fa9592b8dbf8013
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

Loading…