Hydrochloric Acid → HCID 86692840, Verbindung

HRID 928257Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 928257
[CH3:1][C:2]1([CH3:33])[O:6][C@H:5]2[C@H:7]([NH:12][C:13]3[N:18]4[N:19]=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[C:24]([S:28][C:29]([F:32])([F:31])[F:30])[CH:23]=5)[CH:21]=[C:17]4[N:16]=[CH:15][CH:14]=3)[CH2:8][C@H:9]([CH2:10][OH:11])[C@H:4]2[O:3]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[N+]12([S:59]([N-:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])(=[O:61])=[O:60])CCN(CC1)CC2.N12CCN(CC1)CC2.Cl>C(#N)C.O.C(OCC)(=O)C>[C:66]([O:65][C:63](=[O:64])[NH:62][S:59]([O:11][CH2:10][C@@H:9]1[C@@H:4]2[C@@H:5]([O:6][C:2]([CH3:33])([CH3:1])[O:3]2)[CH:7]([NH:12][C:13]2[N:18]3[N:19]=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([S:28][C:29]([F:32])([F:30])[F:31])[CH:23]=4)[CH:21]=[C:17]3[N:16]=[CH:15][CH:14]=2)[CH2:8]1)(=[O:61])=[O:60])([CH3:69])([CH3:67])[CH3:68]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 86692841HCID 86692841, VerbindungHCID 178420725HCID 178420725, Verbindung

Produkt 1

HCID 86692840HCID 86692840, VerbindungAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[(2-{3-(trifluoromethylthio)phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol (3.4 g) was dissolved in 2-methyltetrahedrafuran (32.0 mL) and to this solution was added pyridinium p-toluenesulfonate (3.34 g). This formed a precipitate and to this white slurry was added (4-aza-1-azoniabicyclo[2.2.2]oct-1-ylsulfonyl)(tert-butoxycarbonyl)azanide-1,4-diazabicyclo[2.2.2]octane (1:1) hydrochloride (8.19 g). (prepared according to Armitage, I. et. al. U.S. Patent Application Publication US2009/0036678, and Armitage, I. et. al. Org. Lett., 2012, 14 (10), 2626-2629). The mixture was stirred at ambient temperature until the HPLC showed <1% remaining starting material (about 300 minutes). To the reaction was added ethyl acetate (30 mL) and water (30 mL). After stirring for 10 minutes the phases were separated and the aqueous layer was back extracted with ethyl acetate (30 mL). The organic layers were combined and washed with 10% brine (30 mL) and the layers were separated. The organic layer was then concentrated to dryness to give an off-white solid. The solids were transferred back to the reactor with acetonitrile (35 m L) and stirred for 20 minutes. The solids were isolated by filtration and dried in a vacuum oven at full vacuum overnight (40° C., 16 hours) to give tert-butyl-[({(3aR,4R,6aS)-2,2-dimethyl-6-[(2-{3-(trifluoromethylthio)phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methoxy)sulfonyl]carbamate (3.87 g, 88%). (LCMS: (FA2) M+1 660).

Aufarbeitung

  1. customThis formed a precipitate
  2. custommaterial (about 300 minutes)
  3. stirringAfter stirring for 10 minutes the phases
  4. customwere separated
  5. extractionthe aqueous layer was back extracted with ethyl acetate (30 mL)
  6. washwashed with 10% brine (30 mL)
  7. customthe layers were separated
  8. concentrationThe organic layer was then concentrated to dryness
  9. customto give an off-white solid
  10. stirringstirred for 20 minutes
  11. customThe solids were isolated by filtration
  12. customdried in a vacuum oven at full vacuum overnight (40° C., 16 hours)

Quellen und Nachweise

ORD-Eintrag
ord-a1d4c947a08440239cd432fa7bd0c5eb
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290500B2

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