Hydrochloric Acid → (+/-)-6-({[(1-{2-[3-Fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-methyl-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 639107Notes

Reaction equation

HRID 639107 reaction equation
Cl.[F:2][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][C:17]([CH2:21][NH2:22])([CH3:20])[CH2:16]1)=[N:10][C:9]([O:23][CH3:24])=[CH:8][CH:7]=2.[O:25]=[C:26]1[CH2:31][S:30][C:29]2[CH:32]=[CH:33][C:34]([CH:36]=O)=[N:35][C:28]=2[NH:27]1>CO>[F:2][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][C:17]([CH2:21][NH:22][CH2:36][C:34]3[CH:33]=[CH:32][C:29]4[S:30][CH2:31][C:26](=[O:25])[NH:27][C:28]=4[N:35]=3)([CH3:20])[CH2:16]1)=[N:10][C:9]([O:23][CH3:24])=[CH:8][CH:7]=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 59026083HCID 59026083, compound

Product 1

HCID 11641779(+/-)-6-({[(1-{2-[3-Fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-methyl-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-oneYield 24%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the HCl salt of (±)-[(1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-methyl-3-pyrrolidinyl)methyl]amine (100 mg, 0.257 mmol) in MeOH (3 mL) were added NaHCO (215 mg, 2.57 mmol) followed by 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (51 mg, 0.317 mmol). After 24 h at 25° C., NaBH (15 mg, 0.398 mmol) was added. After 1 h, the reaction was concentrated and the residue was partitioned between DCM-H O. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried over MgSO, concentrated and purified via column chromatography (silica, 4% MeOH in DCM (1% NH OH)) yielding the title compound (30 mg, 24%) as a brown oil: LC/MS (ES) m/e 497 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 8.8 (bs, 1H), 8.65 (s, 1H), 8.22 (d, J=9.0 Hz, 1H), 7.58 (d, J=7.8 Hz, 1H), 7.19 (d, J=9.0 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 4.12 (s, 3H), 3.83 (s, 2H), 3.51 (s, 2H), 3.46-3.50 (m, 2H), 2.9 (m, 4H), 2.5 (m, 3H), 2.3 (m, 1H), 1.85 (m, 1H), 1.55 (m, 1H), 1.1 (s, 3H).

Workup

  1. waitAfter 1 h
  2. concentrationthe reaction was concentrated
  3. customthe residue was partitioned between DCM-H O
  4. extractionThe aqueous phase was extracted several times with DCM
  5. dry with materialthe combined organic fractions were dried over MgSO
  6. concentrationconcentrated
  7. custompurified via column chromatography (silica, 4% MeOH in DCM (1% NH OH))

Sources & evidence

ORD record
ord-5614452172154f59a03da365ea5fe3ef
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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