Methanol → 1-{[(5S,7S)-2-oxo-3-({1-[5-(trifluoromethyl)-3-pyridinyl]-1H-1,2,3-triazol-4-yl}methyl)-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile

HRID 715520Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 715520
[O:1]=[C:2]1[N:6]([CH2:7][C:8]#[CH:9])[CH2:5][C@@:4]2([CH2:14][CH2:13][CH2:12][C@H:11]([CH2:15][N:16]3[C:20]4[CH:21]=[C:22]([C:25]#[N:26])[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH2:10]2)[O:3]1.[N:27]([C:30]1[CH:31]=[N:32][CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)=[N+:28]=[N-:29].[O:40]=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[CH3:53][OH:54]>C(O)(C)(C)C.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].CC#N.O>[C:53]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:54].[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[N:29]=[N:28][N:27]([C:30]3[CH:31]=[N:32][CH:33]=[C:34]([C:36]([F:37])([F:39])[F:38])[CH:35]=3)[CH:9]=2)[CH2:5][C@@:4]2([CH2:14][CH2:13][CH2:12][C@H:11]([CH2:15][N:16]3[C:20]4[CH:21]=[C:22]([C:25]#[N:26])[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH2:10]2)[O:3]1

Komponenten

10

Edukt 4

HCID 887MethanolHCID 212903563-Azido-5-(trifluoromethyl)pyridineHCID 23667548Sodium AscorbateHCID 867175871-{[(5S,7S)-2-oxo-3-(2-propyn-1-yl)-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile

Produkt 2

HCID 6422Trifluoroacetic acidAusbeute 0,1 %HCID 712275731-{[(5S,7S)-2-oxo-3-({1-[5-(trifluoromethyl)-3-pyridinyl]-1H-1,2,3-triazol-4-yl}methyl)-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrileAusbeute 9,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24463Copper sulfate pentahydrateKatalysatorHCID 962WaterLösungsmittel2×HCID 6386tert-ButanolLösungsmittelHCID 18373917Acetonitrile--water (1/1)Lösungsmittel

Versuchsvorschrift

To a light orange solution of 1-{[(5S,7S)-2-oxo-3-(2-propyn-1-yl)-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile (0.100 g, 0.287 mmol) (93:7 trans:cis) in tert-butanol (1.435 mL) and water (1.435 mL) in a vial was added 3-azido-5-(trifluoromethyl)pyridine (0.054 g, 0.287 mmol), sodium L-ascorbate (0.011 g, 0.057 mmol), copper(II) sulfate pentahydrate (0.014 g, 0.057 mmol), and water (1.435 mL). After 18 h, 1 mL of MeOH was added and the mixture was vacuum filtered using a small Buchner funnel. The filtrate was filtered through Acrodisc CR 25 mm syringe filter with 0.2 um PTFE membrane and purified by Gilson prep HPLC: 25-45% CH3CN/H2O, 0.1% TFA, 30×150 mm Sunfire C18, 25 mL/min, 15 min to yield the TFA salt of 1-{[(5S,7S)-2-oxo-3-({1-[5-(trifluoromethyl)-3-pyridinyl]-1H-1,2,3-triazol-4-yl}methyl)-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile as an orange foam (18.1 mg, 9.2% yield). MS (m/z) 537 (M+H+).

Aufarbeitung

  1. filtrationfiltered
  2. filtrationThe filtrate was filtered through Acrodisc CR 25 mm syringe
  3. filtrationfilter with 0.2 um PTFE membrane
  4. custompurified by Gilson prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-40988763f0e641c99faeb3580029e5e0
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09187464B2

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