Potassium Sodium Tartrate → tert-Butyl (3S)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)azepane-1-carboxylate

HRID 30338

반응식

HRID 30338 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([NH:14][C:15]([NH:17]C(=O)C(Cl)(Cl)Cl)=[O:16])=[C:11]([C:24]([O:26]C)=O)[CH:10]=2)=[CH:5][CH:4]=1.C[Al](C)C.[C:32]([O:36][C:37]([N:39]1[CH2:45][CH2:44][CH2:43][CH2:42][C@H:41]([NH2:46])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.CCOC(C)=O.O>[NH2:17][C:15]([NH:14][C:12]1[S:13][C:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[CH:10][C:11]=1[C:24]([NH:46][C@H:41]1[CH2:42][CH2:43][CH2:44][CH2:45][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:40]1)=[O:26])=[O:16]

참가 물질

8

반응물 4

HCID 9357Potassium Sodium TartrateHCID 11546916Methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylateHCID 16682925TrimethylaluminumHCID 34178419tert-Butyl (3S)-3-aminoazepane-1-carboxylate

생성물 1

HCID 69271799tert-Butyl (3S)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)azepane-1-carboxylate수율 62%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

실험 절차

To a solution of methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylate (1.36 g, 3 mmol) in anhydrous THF (20 mL) was added a solution of [Me2Al-3-Boc-(S)-3-aminohomopiperidine] in THF (preformed by the careful addition of Me3Al (2.0 M in hexanes, 3.0 mL, 6.0 mmol) to a solution of (S)-3-amino-azepane-1-carboxylic acid tert-butyl ester in 10 nL of THF at −78° C. followed by warming to room temperature under nitrogen and stirring for an additional 15 min.). The resulting deep yellow/orange solution was stirred overnight at room temperature. The reaction mixture was cooled with ice and a 10% aqueous solution of Rochelle's salt was added slowly to quench the reaction. The resulting biphasic solution was warmed to room temperature and stirred for an additional 1 h. The mixture was diluted with EtOAc and H2O, the aqueous layer was extracted with EtOAc (3×) and the combined organic extracts were washed with H2O, brine and dried (Na2SO4). Evaporation gave a pale orange solid. Purification by ISCO MPLC (SiO2, 60-80% EtOAc/hexanes) gave 0.9 g (62%) of the title compound as a white solid. 1H NMR (d6-DMSO, δ 11.0, s, 1H, δ 7.95, d, 0.5H, δ 7.81, d, 0.5H, δ 7.65, s, 0.5H; δ 7.56, s, 0.5H; δ 7.46, d, 2H; δ 6.97, d, 2H; δ 6.96, br s, 2H; δ 4.19, m, 0.5H; δ 4.11, m, 0.5H; δ 3.77, m, 3H; δ 3.65, m, 1H; δ 3.48, m, 1H; δ 3.20, m, 2H; δ 1.75, m, 3H; δ 1.58, m, 2H; δ 1.42, s, 4.5H; δ 1.39, m, 1H; δ 1.36, s, 4.5H), LC/MS (APCI, ES, M+H=489).

후처리

  1. stirringThe resulting deep yellow/orange solution was stirred overnight at room temperature
  2. temperatureThe reaction mixture was cooled with ice
  3. customto quench
  4. customthe reaction
  5. temperatureThe resulting biphasic solution was warmed to room temperature
  6. stirringstirred for an additional 1 h
  7. extractionthe aqueous layer was extracted with EtOAc (3×)
  8. washthe combined organic extracts were washed with H2O, brine
  9. dry with materialdried (Na2SO4)
  10. customEvaporation
  11. customgave a pale orange solid
  12. customPurification by ISCO MPLC (SiO2, 60-80% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-faa03acd8fc34029bfe698c8ef0a149b
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423061B2

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