Tris(hydroxymethyl)aminomethane → HCID 66854553, Verbindung

HRID 252109

Reaktionsgleichung

Reaktionsgleichung von HRID 252109
[F:1][C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]2)=[CH:4][CH:3]=1.[S:14]1[CH:18]=[C:17](C=O)[C:16]2[CH:21]=[CH:22][CH:23]=[CH:24][C:15]1=2.[CH2:25](O)C(N)(CO)CO.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(O)C.CO>[S:14]1[CH:18]=[C:17]([N:13]([CH3:25])[C@H:10]2[CH2:11][CH2:12][N:8]([C:5]3[CH:6]=[N:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH2:9]2)[C:16]2[CH:21]=[CH:22][CH:23]=[CH:24][C:15]1=2

Komponenten

8

Edukt 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 2273281-Benzothiophene-3-carbaldehydeHCID 4311764Sodium borohydrideHCID 66854646HCID 66854646, Verbindung

Produkt 1

HCID 66854553HCID 66854553, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittel2×

Versuchsvorschrift

Mix an aliquot (1 mL) of a 0.25 M solution of (S)-[1-(6-fluoropyridin-3-yl)-pyrrolidin-3-yl]-amine (0.25 mmol) in toluene, an aliquot (1 mL) of a 1.0 M solution of benzo[b]thiophene-3-carboxaldehyde (1.0 mmol) in toluene and add a single activated 4 Å molecular sieve. Stir the reactants at room temperature in air. After 16 h add PS-Trisamine (1.5 mmol) and another single activated 4 Å molecular sieve. Stir the reactants at room temperature in air. After 24 h filter the reaction solution to remove the PS-Trisamine, and add an aliquot (2 mL) of a 0.25 M solution of sodium borohydride (0.5 mmol) in ethanol. Stir the reactants at room temperature in air. After 48 h add methanol (2 mL) to the reactants and agitate vigorously. Remove the excess reactants by ion-exchange chromatography using a 5 g SCX-2 cartridge (0.5 mmol/g SO3H) by wetting it with one column volume of methanol. Apply the mixture to the cartridge and allow it to percolate through the stationary phase (under gravity) into a vial. Wash the cartridge with one column volume of methanol such that these washings also pass into the vial. Replace with a second vial and elute with 3.5N ammonia in methanol (10 mL). Evaporate the solvents from the ammonia washings on a heating block under a stream of nitrogen to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.90-7.98 (2H, m), 7.57 (1H, s), 7.39-7.42 (1H, m), 7.35-7.39 (2H, m), 7.08-7.13 (1H, m), 6.96 (1H, dd, J=8.93, 3.30 Hz), 4.01 (2H, s), 3.43-3.50 (2H, m), 3.20-3.27 (1H, m), 3.17 (1H, d, J=5.14 Hz), 3.07-3.13 (1H, m), 2.10-2.18 (1H, m), 1.87-1.95 (1H, m), MS (ES): m/z=328 [M+H].

Aufarbeitung

  1. stirringStir the reactants at room temperature in air
  2. filtrationAfter 24 h filter the reaction solution
  3. customto remove the PS-Trisamine
  4. stirringStir the reactants at room temperature in air
  5. stirringagitate vigorously
  6. customRemove the excess reactants by ion-exchange chromatography
  7. washWash the cartridge with one column volume of methanol such that these washings
  8. washReplace with a second vial and elute with 3.5N ammonia in methanol (10 mL)
  9. customEvaporate the solvents from the ammonia washings on a heating block under a stream of nitrogen

Quellen und Nachweise

ORD-Eintrag
ord-9cc288b5d4b04346bbec59acbfae7efc
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07868014B2

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