Potassium Carbonate → 9-benzyloxy-6-(5-chloro-3'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169415Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2169415
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2Br)[N:11]2[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28](=[O:29])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[C:38]2[CH:37]=[CH:36][CH:35]=[C:34]([F:33])[CH:39]=2)[N:11]2[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28](=[O:29])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867260459-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Produkt 1

HCID 867260479-benzyloxy-6-(5-chloro-3'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneAusbeute 63,04 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

In a sealed tube was placed a stirred solution of 9-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (380) (100 mg, 0.194 mmol) in dioxane (3 mL), 3-fluorophenyl boronicacid (27.132 mg, 0.194 mmol), and a 1N solution of potassium carbonate [(80.349 mg, 0.581 mmol) dissolved in 1.06 mL water] was added at room temperature. The reaction mixture was de-gassed with argon by purging for 30 min. Pd(triphenyl phosphine)4 (22.395 mg, 0.019 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (15.911 mg, 0.039 mmol) were added and the reaction mixture was further degassed for another 10 min. The reaction mixture was heated for 30 min at 80° C. (while progress of the reaction was monitored by LC-MS). The reaction was filtered and diluted with water (5 mL) and extract with ethyl acetate (2×20 mL). The combined extracts were dried and concentrated. The resulting crude product was purified by column (using amine bound silica gel) to get 9-benzyloxy-6-(5-chloro-3′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (383) (65 mg, 63.04%) as an off-white solid.

Aufarbeitung

  1. customIn a sealed tube was placed
  2. customThe reaction mixture was de-gassed with argon
  3. customby purging for 30 min
  4. customthe reaction mixture was further degassed for another 10 min
  5. filtrationThe reaction was filtered
  6. additiondiluted with water (5 mL)
  7. extractionextract with ethyl acetate (2×20 mL)
  8. customThe combined extracts were dried
  9. concentrationconcentrated
  10. customThe resulting crude product was purified by column (using amine bound silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-9818d62c17c8455cbce0fd52087193ea
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045486B2

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