Acetonitrile → 2,2-Dimethyl-propionic acid 5-{3-[hydroxy-(3-trifluoromethyl-pyridin-2-yl)-methyl]-phenyl}-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

HRID 886577Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 886577
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[N:10]=1.Br[C:36]1[CH:37]=[C:38]([CH:42]([C:44]2[C:49]([C:50]([F:53])([F:52])[F:51])=[CH:48][CH:47]=[CH:46][N:45]=2)[OH:43])[CH:39]=[CH:40][CH:41]=1.C(#N)C.C(=O)(O)[O-].[Na+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].ClCCl.C1(C)C=CC=CC=1>[OH:43][CH:42]([C:44]1[C:49]([C:50]([F:53])([F:51])[F:52])=[CH:48][CH:47]=[CH:46][N:45]=1)[C:38]1[CH:37]=[C:36]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:31])([CH3:32])[CH3:33])[C:12]3=[N:13][CH:14]=2)[CH:41]=[CH:40][CH:39]=1

Komponenten

8

Edukt 4

HCID 6342AcetonitrileHCID 516892Sodium Bicarbonate2×HCID 59824996(3-Bromo-phenyl)-(3-trifluoromethyl-pyridin-2-yl)-methanolHCID 598250492,2-Dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

Produkt 1

HCID 598250482,2-Dimethyl-propionic acid 5-{3-[hydroxy-(3-trifluoromethyl-pyridin-2-yl)-methyl]-phenyl}-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl esterAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 53485975CID 53485975KatalysatorHCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

465 mg (1.00 mmol) of 2,2-dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester, 50 mg (61 μmol) of dichloro[1,1′-bis(diphenyl-phoshino)ferrocene]palladium(II) dichloromethane adduct and 340 mg (1.02 mmol) of (3-bromo-phenyl)-(3-trifluoromethyl-pyridin-2-yl)-methanol were place in a microwave vial. 8 mL of acetonitrile, 3 mL of toluene and 8 mL of a saturated aqueous solution of sodium bicarbonate were added. The vial was sealed and the resulting mixture heated in an oil bath to 65° C. for 22 h. The resulting mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous layer was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulfate and evaporated. The resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 388 mg (0.66 mmol, 66%) of 2,2-dimethyl-propionic acid 5-{3-[hydroxy-(3-trifluoromethyl-pyridin-2-yl)-methyl]-phenyl}-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester as a beige solid. 1H NMR (500 MHz, DMSO-d6) α 8.90 (d, 1H), 8.86 (d, 1H), 8.34 (d, 1H), 8.20 (d(d), 1H), 7.81 (s, 1H), 7.67-7.64 (m, 2H), 7.56-7.50 (m, 2H), 7.45 (t, 1H), 7.39 (d, 1H), 7.27 (d, 1H), 7.13 (t, 1H), 6.51 (s, 2H), 6.26 (d, 1H), 6.11 (d, 1H), 3.86 (s, 3H), 1.12 (s, 9H); MS: m/z 591.1 (M+H+), 613.1 (M+Na+).

Aufarbeitung

  1. customThe vial was sealed
  2. extractionThe aqueous layer was extracted twice with dichloromethane
  3. dry with materialthe combined organic phases were dried over sodium sulfate
  4. customevaporated
  5. customThe resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-9d94e08a2dc74580bf148291ec2df55c
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242280B2

Notizen zur Reaktion

Wird geladen…