Hydrochloric Acid → tert-butyl methyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methylpiperidine-3,4-diyl]biscarbamate

HRID 924521ノート

反応式

HRID 924521 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@@H:14]([NH:15][C:16]([O:18][CH3:19])=[O:17])[C@@H:13]([CH3:20])[CH2:12][N:11]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[N:27](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.O1CCOCC1.CCN(C(C)C)C(C)C.C(OC(ON1C(=O)CCC1=O)=O)(C)(C)C>>[NH2:27][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:21]=1[N:11]1[CH2:12][C@H:13]([CH3:20])[C@H:14]([NH:15][C:16](=[O:17])[O:18][CH3:19])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1

参加物

6

反応物 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 83168Carbonic acid, 1,1-dimethylethyl 2,5-dioxo-1-pyrrolidinyl esterHCID 86726959Di-tert-butyl (4-{(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-4-[(methoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonate

生成物 1

HCID 86726962tert-butyl methyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methylpiperidine-3,4-diyl]biscarbamate収率 76%

実験手順

A mixture of di-tert-butyl (4-{(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-4-[(methoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonate (1.41 g, 2.43 mmol) and 4.0 M HCl in dioxane (40.0 mL, 1.60E2 mmol) was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure and the solid was dried under high vacuum for 10 min. DCM (25.0 mL) was added to the residue, followed by DIPEA (1.94 g, 15.0 mmol) and 1-[(tert-butoxycarbonyl)oxy]pyrrolidine-2,5-dione (579 mg, 2.69 mmol). The mixture was then stirred room temperature for 16 h, then concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aq. Na2CO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (40 g, eluting with 100% EtOAc, then 10% MeOH in DCM with 1% Et3N) to give the sub-title compound as a yellow foamy solid (701 mg, 76%). LCMS calc. for C18H30N5O4 (M+H)+: m/z=380.2. Found: 380.3.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe solid was dried under high vacuum for 10 min
  3. additionDCM (25.0 mL) was added to the residue
  4. stirringThe mixture was then stirred room temperature for 16 h
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with saturated aq. Na2CO3 and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography on silica gel (40 g
  12. washeluting with 100% EtOAc

出典と根拠

ORDレコード
ord-d3e2c816106c4b6a8bbc5e7b48862688
出典データセット
uspto-grants-2016_03
特許番号
US09278950B2

反応ノート

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