Hydrochloric Acid → HCID 11648608, compound

HRID 1992516Notes

Reaction equation

HRID 1992516 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9](=[O:29])[N:10]([CH:12]1[CH2:16][CH2:15][N:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[N:25]=3)[N:20]=[CH:19][CH:18]=2)[CH2:13]1)[CH3:11])(C)(C)C.Cl.C(N(CC)CC)C.[O:39]=[C:40]1[CH2:45][O:44][C:43]2[CH:46]=[CH:47][C:48]([CH:50]=O)=[N:49][C:42]=2[NH:41]1.[BH4-].[Na+].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.O1CCOCC1.CO.ClCCl.CO>[CH3:11][N:10]([CH:12]1[CH2:16][CH2:15][N:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[N:25]=3)[N:20]=[CH:19][CH:18]=2)[CH2:13]1)[C:9](=[O:29])[CH2:8][NH:7][CH2:50][C:48]1[CH:47]=[CH:46][C:43]2[O:44][CH2:45][C:40](=[O:39])[NH:41][C:42]=2[N:49]=1

Participants

11

Reactant 6

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 58955143HCID 58955143, compound

Product 1

HCID 11648608HCID 11648608, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6212ChloroformSolvent2×HCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

({[1-(6-Methoxy-[1,5]naphthyridin-4-yl)-pyrrolidin-3-yl]-methyl-carbamoyl}-methyl)-carbamic acid tert-butyl ester (272 mg, 0.66 mmol) was dissolved in a minimum amount of chloroform and treated with 4N HCl in dioxane (3 mL). After stirring 1 h, the reaction mixture was concentrated to dryness and azeotroped with toluene. The resulting HCl salt (302 mg, 0.66 mmol) was dissolved in methanol/dichloromethane (8 mL, 1:3) and treated with triethylamine (0.46 mL, 3.3 mmol) and 3-Oxo-3,4-dihydro-2H -pyrido[3,2-b ][1,4]oxazine-6-carbaldehyde (117 mg, 0.66 mmol) and stirred for 72 hours. The solution was diluted with a small amount of methanol and treated with sodium borohydride (25 mg, 0.66 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 a di-HCl salt of the title compound as an off-white solid (27 mg, 8.6%): LC-MS m/z 478 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 8.25 (d, 1H, J=6 Hz), 8.02 (d, J=9 Hz, 1H), 7.29 (m, 1H), 7.11 (d, J=9 Hz, 1H), 6.99 (d, J=8 Hz, 1H), 6.62 (d, J=6 Hz, 1H), 5.23 (m, 1H), 4.63 (m, 2H), 4.18 (m, 3H), 4.01 (m, 3H), 3.81 (m, 2H), 3.68 (s, 1H), 3.57 (s, 1H), 3.00 (s, 2H), 2.26 (m, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated to dryness
  2. customazeotroped with toluene
  3. stirringstirred for 72 hours
  4. stirringAfter stirring 90 minutes
  5. extractionThe aqueous layer was extracted with chloroform
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed in chloroform/methanol/ammonia

Sources & evidence

ORD record
ord-1d60f86360b8448ab655171c6b8c2780
Source dataset
uspto-grants-2010_01
Patent number
US07648984B2

Reaction notes

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