Sulfuric acid magnesium salt (1:1) → (4s)-N-(5-Bromo-6-chloropyridin-3-yl)-1-azatricyclo[3.3.1.13,7]decan-4-amine 4-methylbenzenesulfonate

HRID 1878679ノート

反応式

HRID 1878679 の反応式
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]

参加物

9

反応物 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

生成物 1

HCID 86621456(4s)-N-(5-Bromo-6-chloropyridin-3-yl)-1-azatricyclo[3.3.1.13,7]decan-4-amine 4-methylbenzenesulfonate

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒3 回

反応条件

温度
-10 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-fb2f240180c5478585bb7fdfeeaf87c2
出典データセット
uspto-grants-2012_11
特許番号
US08314119B2

反応ノート

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