Sodium Bicarbonate → HCID 86679273, Verbindung

HRID 1519707Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1519707
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]#[C:24][C:25]2[CH:50]=[CH:49][C:28]([C:29]([N:31]([CH3:48])[C@:32]([CH3:47])([C:37]([NH:39][O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)=[O:38])[C:33]([NH:35][CH3:36])=[O:34])=[O:30])=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)=O.Cl.[F:52][CH2:53][CH2:54][O:55][CH:56]1[CH2:59][NH:58][CH2:57]1.C(=O)([O-])O.[Na+]>CN1C(=O)CCC1.C(OCC)(=O)C.O>[F:52][CH2:53][CH2:54][O:55][CH:56]1[CH2:59][N:58]([CH2:15][C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][C:25]3[CH:26]=[CH:27][C:28]([C:29]([N:31]([CH3:48])[C@:32]([CH3:47])([C:37]([NH:39][O:40][CH:41]4[CH2:46][CH2:45][CH2:44][CH2:43][O:42]4)=[O:38])[C:33]([NH:35][CH3:36])=[O:34])=[O:30])=[CH:49][CH:50]=3)=[CH:21][CH:22]=2)[CH2:57]1

Komponenten

8

Edukt 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 768479003-(2-Fluoroethoxy)azetidine hydrochlorideHCID 86679270(2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

Produkt 1

HCID 86679273HCID 86679273, VerbindungAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

Sodium triacetoxyborohydride (0.10 g) was added to a solution in NMP (1.5 mL) of (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.15 g) as obtained in Example 16-(1) and 3-(2-fluoroethoxy)azetidine hydrochloride (63 mg) as obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere. The mixture was stirred for 40 minutes at room temperature. Water and ethyl acetate were added, and the mixture was adjusted to pH 7.5 with a saturated aqueous solution of sodium hydrogen carbonate, whereafter the organic layer was isolated. The extract was washed with brine, and dried over anhydrous sodium sulfate. Then, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=80/20→50/50) to obtain (2S)-2-[{4-[(4-{[3-(2-fluoroethoxy)azetidin-1-yl]methyl}phenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow oil) (0.14 g, 81%).

Aufarbeitung

  1. customas obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere
  2. customwas isolated
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThen, the desiccant was filtered out
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=80/20→50/50)

Quellen und Nachweise

ORD-Eintrag
ord-177d3f4d07e44c329c5dc317a601b186
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073821B2

Notizen zur Reaktion

Wird geladen…