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

HRID 30338
Notes
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Reaction equation

HRID 30338 reaction equation
[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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-faa03acd8fc34029bfe698c8ef0a149b
Source dataset
uspto-grants-2008_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07423061B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes