Sulfuric acid magnesium salt (1:1) → HCID 86621456, compound

HRID 878452Notes

Reaction equation

HRID 878452 reaction equation
S([O-])([O-])(=O)=O.[Mg+2].[Br:7][C:8]1[CH:9]=[C:10]([NH2:15])[CH:11]=[N:12][C:13]=1[Cl:14].[N:16]12[CH2:25][CH:20]3[CH2:21][CH:22]([CH2:24][CH:18]([C:19]3=O)[CH2:17]1)[CH2:23]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O.[CH3:42][C:43]1[CH:48]=[CH:47][C:46]([S:49]([OH:52])(=[O:51])=[O:50])=[CH:45][CH:44]=1>C(O)(=O)C.C(OCC)(=O)C.CCO>[CH3:42][C:43]1[CH:44]=[CH:45][C:46]([S:49]([OH:52])(=[O:51])=[O:50])=[CH:47][CH:48]=1.[Br:7][C:8]1[CH:9]=[C:10]([NH:15][C@@H:19]2[CH:20]3[CH2:25][N:16]4[CH2:23][CH:22]([CH2:24][CH:18]2[CH2:17]4)[CH2:21]3)[CH:11]=[N:12][C:13]=1[Cl:14]

Participants

9

Reactant 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 1426421-Azatricyclo(3.3.1.1,3,7)decan-4-oneHCID 521998p-Toluenesulfonic acid monohydrateHCID 5049666Sodium triacetoxyborohydrideHCID 145952215-Bromo-6-chloropyridin-3-amine

Product 1

HCID 86621456HCID 86621456, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
-10 °C

Procedure

Magnesium sulfate (1.80 g, 15 mmol) and 5-bromo-6-chloropyridin-3-amine (310 mg, 1.49 mmol) were added to a solution of 1-azatricyclo[3.3.1.13,7]decan-4-one (151 mg, 1.00 mmol) in acetic acid (5 mL). The resulting suspension was stirred for 10 minutes, then sodium triacetoxyborohydride (412 mg, 1.94 mmol) was added. The mixture was stirred at room temperature for 14 hours, then concentrated under vacuum to dryness. The white solid residue was slurried in ethyl acetate (3 mL), applied to the top of a silica column and eluted with chloroform-methanol-concentrated ammonium hydroxide (90:10:1) to provide a pink solid. This material was heated with ethyl acetate (3 mL) and a solution of 4-methylbenzenesulfonic acid monohydrate (40 mg, 1 eq.) in warm ethyl acetate (1 mL) was added. Additional ethyl acetate (3 mL) and EtOH (3 mL) were added with heating to bring the mixture to homogeneity. After cooling to room temperature and finally to −10° C., the mixture was filtered and the collected solid was washed with ethyl acetate (3 mL) and dried under vacuum to provide the titled compound: 1H NMR (300 MHz, methanol-D4) δ 1.91 (br d, J=13.1 Hz, 2H), 2.11-2.21 (m, 1H), 2.22-2.32 (m, 4H), 2.36 (s, 3H), 3.54 (s, 2H), 3.59-3.72 (m, 4H), 3.91 (s, 1H), 7.23 (d, J=7.9 Hz, 2H), 7.47 (d, J=2.8 Hz, 1H), 7.70 (d, J=8.3 Hz, 2H), 7.85 ppm (d, J=2.8 Hz, 1H); MS DCI/NH3 m/z 342/344/346 (M+H)+; Anal. Calcd for C14H17N3ClBr. C7H8O3S: C, 48.99; H, 4.89; N, 8.16. Found: C, 48.95; H, 4.66; N, 8.02.

Workup

  1. stirringThe mixture was stirred at room temperature for 14 hours
  2. concentrationconcentrated under vacuum to dryness
  3. washeluted with chloroform-methanol-concentrated ammonium hydroxide (90:10:1)
  4. customto provide a pink solid
  5. temperaturewith heating
  6. filtrationthe mixture was filtered
  7. washthe collected solid was washed with ethyl acetate (3 mL)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-ecc34ecba6204560ba672f628762d6d5
Source dataset
uspto-grants-2015_03
Patent number
US08987453B2

Reaction notes

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