Sodium Carbonate → tert-Butyl {(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-ethylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate

HRID 1842610Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1842610
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([O:11][CH:12]([F:14])[F:13])[CH:8]=[N:7][C:6]=12.[C:15]([O:19][C:20](=[O:49])[NH:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][C:24]([F:29])([F:28])[C@@H:23]1[NH:30][C:31]([C:33]1[S:34][C:35]([CH2:47][CH3:48])=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:37]=1)=[O:32])([CH3:18])([CH3:17])[CH3:16].C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[C:15]([O:19][C:20](=[O:49])[NH:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][C:24]([F:29])([F:28])[C@@H:23]1[NH:30][C:31]([C:33]1[S:34][C:35]([CH2:47][CH3:48])=[C:36]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[C:9]([O:11][CH:12]([F:14])[F:13])[CH:8]=[N:7][C:6]=23)[CH:37]=1)=[O:32])([CH3:18])([CH3:17])[CH3:16]

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 673254323-Bromo-6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidineHCID 89750975tert-Butyl[(1R,2R)-2-({[5-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate

Produkt 1

HCID 68304376tert-Butyl {(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-ethylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamateAusbeute 56,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

3-Bromo-6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidine (0.030 g, 0.114 mmol), tert-butyl[(1R,2R)-2-({[5-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate (0.059 g, 0.115 mmol), Pd(PPh3)4 (6.57 mg, 0.007 mmol), and 2 M Na2CO3 (aq) (0.170 mL, 0.341 mmol) were placed in a sealed tube and DMF (1.14 mL) added. The mixture was purged with N2 for 5 min. The reaction was heated to 85° C. for 16 h. The mixture was cooled to room temperature, diluted with dichloromethane, and washed twice with saturated sodium bicarbonate (aq) and once with brine. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (0-70% EtOAc/Hex) to give the title compound (0.037 g, 0.064 mmol). LRMS (APCI) calc'd for (C25H29F4N5O4S) [M+H]+, 572.2; found 572.1.

Aufarbeitung

  1. customThe mixture was purged with N2 for 5 min
  2. temperatureThe mixture was cooled to room temperature
  3. additiondiluted with dichloromethane
  4. washwashed twice with saturated sodium bicarbonate (aq) and once with brine
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (0-70% EtOAc/Hex)

Quellen und Nachweise

ORD-Eintrag
ord-9a053bb8a9e34136b024e380d4c5514c
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946237B2

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