Hydrochloric Acid → HCID 11569250, compound

HRID 1992525Notes

Reaction equation

HRID 1992525 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH2:17][CH2:16][CH:15]([S:18][CH2:19][CH2:20][NH:21][C:22](=O)OC(C)(C)C)[CH2:14]1.Cl.C(N(CC)CC)C.[O:37]=[C:38]1[CH2:43][S:42][C:41]2[CH:44]=[CH:45][C:46](C=O)=[N:47][C:40]=2[NH:39]1.[BH4-].[Na+].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.O1CCOCC1.CO>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH2:17][CH2:16][CH:15]([S:18][CH2:19][CH2:20][NH:21][CH2:22][C:46]2[CH:45]=[CH:44][C:41]3[S:42][CH2:43][C:38](=[O:37])[NH:39][C:40]=3[N:47]=2)[CH2:14]1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 58955130HCID 58955130, compound

Product 1

HCID 11569250HCID 11569250, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

1,1-dimethylethyl [2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]carbamate (210 mg, 0.52 mmol) was dissolved in a minimum amount of chloroform and treated with 4N HCl in dioxane (2 mL). After stirring 2 h, the reaction mixture was concentrated to dryness and azeotroped with toluene. The resulting HCl salt of the free amine was dissolved in methanol/dichloromethane (4 mL, 1:3) and treated with triethylamine (0.36 mL, 2.6 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (101 mg, 0.52 mmol) and stirred for 12 hours. The solution was diluted with a small amount of methanol and treated with sodium borohydride (19 mg, 0.52 mmol.) After stirring 90 minutes, the reaction mixture was diluted with chloroform and poured into saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with chloroform. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated and chromatographed in chloroform/methanol/ammonia. The resulting solid was converted to an HCl salt of the title compound as a yellow solid (85 mg, 34%): LC-MS m/z 483 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 8.27-8.31 (m, 1H), 8.18-8.22 (m, 1H), 7.82-7.86 (m, 1H), 7.35-7.41 (m, 1H), 7.16-7.19 (m, 1H), 6.89-6.94 (m, 1H), 7.39-7.42 (m, 2H), 4.2-4.27 (m, 1H), 4.14 (s, 3H), 3.84-3.98 (m, 3H), 3.69-3.75 (m, 1H), 3.55 (s, 2H), 3.42-3.50 (m, 2H), 3.16-3.26 (m, 2H), 2.55-2.63 (m, 1H), 2.18-2.22 (m, 1H).

Workup

  1. concentrationthe reaction mixture was concentrated to dryness
  2. customazeotroped with toluene
  3. dissolutionThe resulting HCl salt of the free amine was dissolved in methanol/dichloromethane (4 mL, 1:3)
  4. stirringstirred for 12 hours
  5. stirringAfter stirring 90 minutes
  6. extractionThe aqueous layer was extracted with chloroform
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed in chloroform/methanol/ammonia

Sources & evidence

ORD record
ord-4996e8774e7f4fcba8f1be8ebc1dcfb9
Source dataset
uspto-grants-2010_01
Patent number
US07648984B2

Reaction notes

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