1-Isopropylpiperazine → 2-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

HRID 880391

Reaktionsgleichung

Reaktionsgleichung von HRID 880391
[CH:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].Br[CH2:11][C:12]1[O:16][C:15]([C:17]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]3[C:18]=2[CH:19]=[N:20][N:21]3[S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)(=[O:29])=[O:28])=[N:14][CH:13]=1.C([N-]CC)C>CS(C)=O>[Cl:26][C:24]1[CH:23]=[C:22]2[C:18]([CH:19]=[N:20][N:21]2[S:27]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)(=[O:29])=[O:28])=[C:17]([C:15]2[O:16][C:12]([CH2:11][N:7]3[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]3)=[CH:13][N:14]=2)[CH:25]=1

Komponenten

5

Edukt 3

HCID 780131-IsopropylpiperazineHCID 7566642DiethylamideHCID 595647134-[5-(Bromomethyl)-1,3-oxazol-2-yl]-6-chloro-1-(phenylsulfonyl)-1H-indazole

Produkt 1

HCID 595647082-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

DMSO (7 vols, 70 ml) and isopropylpiperazine (1.5 eq, 0.387 wt, 0.431 vol, 4.31 ml, 3.87 g) are charged to a clean vessel. 5-(Bromomethyl)-2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)oxazole (1.0 eq, 10 g (9.13 g corrected for assay), 1 wt) is added in 5 portions at 20° C. over 1 hr and the mixture stirred for 1 hr. The mixture is heated to 50° C. and aged for 1 hr, then checked for consumption of starting material by HPLC. Diethylamide (1.2 eq, 0.244 wt, 0.336 vol, 2.44 g, 3.36 ml) is added over 10 mins and the mixture aged for 30 mins, then cooled to 20° C. over 1 hr and further aged for 2 hrs. The thick slurry is filtered and washed with DMSO (2×1.5 vols, 2×15 ml) followed by acetone:water 1:2 (3×2 vols, 3×20 ml). The resultant solid is blown dry on the filter and dried at 60° C. in vacuo to constant weight/temperature to afford 2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole as an off-white solid.

Aufarbeitung

  1. customchecked for consumption of starting material by HPLC
  2. waitthe mixture aged for 30 mins
  3. temperaturecooled to 20° C. over 1 hr
  4. waitfurther aged for 2 hrs
  5. filtrationThe thick slurry is filtered
  6. washwashed with DMSO (2×1.5 vols, 2×15 ml)
  7. customThe resultant solid is blown dry on the
  8. filtrationfilter
  9. customdried at 60° C. in vacuo to constant weight/temperature

Quellen und Nachweise

ORD-Eintrag
ord-58b9d54779234826ba15017a62aea86f
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993576B2

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