Triethylamine → (R)-tetrahydrofuran-3-yl-4-(3-(5-fluoro-2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

HRID 1478290Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1478290
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]4[CH2:24][CH2:23][O:22][CH2:21]4)=[O:18])[CH2:13][CH2:12]3)=[N:7][C:6]=12.[F:25][C:26]1[CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[C:29]([O:32][CH3:33])=[N:30][CH:31]=1.C(N(CC)CC)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[F:25][C:26]1[CH:27]=[C:28]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]5[CH2:24][CH2:23][O:22][CH2:21]5)=[O:18])[CH2:13][CH2:12]4)=[N:7][C:6]=23)[C:29]([O:32][CH3:33])=[N:30][CH:31]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467397215-Fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86697452(R)-tetrahydrofuran-3-yl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

Produkt 1

HCID 86697455(R)-tetrahydrofuran-3-yl-4-(3-(5-fluoro-2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylateAusbeute 27,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

(R)-tetrahydrofuran-3-yl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate (100 mg, 0.25 mmol), 5-fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (127 mg, 0.5 mmol), triethylamine (211 uL, 1.5 mmol), Pd(OAc)2 (1 mg, 0.0025 mmol), and x-Phos (5 mg, 0.005 mmol) were taken up in 4 mL dioxane and 1 mL water under nitrogen and stirred at 85° C. for 2 hours. Reaction then cooled to room temperature, filtered through celite plug with acetonitrile and DCM. Reduced in vacuo and purified on Shimadzu neutral phase prep, lyopholized to get 30 mg product. 1H NMR (400 MHz, DMSO-d6) d 8.80 (d, J=7.83 Hz, 1H), 8.72 (dd, J=3.03, 10.36 Hz, 1H), 8.56 (s, 1H), 7.94 (d, J=3.03 Hz, 1H), 6.86 (d, J=7.83 Hz, 1H), 5.18 (d, J=1.77 Hz, 1H), 4.00 (s, 3H), 3.71-3.83 (m, 8H), 3.32 (s, 2H), 2.08 (s, 1H), 2.13 (s, 1H), 1.89-2.00 (m, 1H) LRMS (ESI) m/z 443 [(M+H)]+, calc'd for C21H23FN6O4: 442.45.

Aufarbeitung

  1. customReaction
  2. filtrationfiltered through celite plug with acetonitrile and DCM
  3. custompurified on Shimadzu neutral phase prep

Quellen und Nachweise

ORD-Eintrag
ord-80bee015a45d4a189cfd439d5f8382b4
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403832B2

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