Ammonia → 3-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2,5-bis(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide

HRID 419419Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419419
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[N:34]1([CH:40]2[CH2:45][CH2:44][N:43]([C:46]3[C:52]([O:53][CH3:54])=[CH:51][C:49]([NH2:50])=[C:48]([O:55][CH3:56])[CH:47]=3)[CH2:42][CH2:41]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.N>CC(O)C.Cl.CO>[N:34]1([CH:40]2[CH2:41][CH2:42][N:43]([C:46]3[C:52]([O:53][CH3:54])=[CH:51][C:49]([NH:50][C:2]4[N:7]=[C:6]([C:8]5[N:12]6[CH:13]=[CH:14][CH:15]=[CH:16][C:11]6=[N:10][C:9]=5[C:17]5[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=5)[C:20]([NH:22][C:23]5[C:24]([F:30])=[CH:25][CH:26]=[CH:27][C:28]=5[F:29])=[O:21])[CH:5]=[CH:4][N:3]=4)=[C:48]([O:55][CH3:56])[CH:47]=3)[CH2:44][CH2:45]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Komponenten

7

Edukt 3

HCID 222AmmoniaHCID 594526104-(1,4'-Bipiperidin-1'-yl)-2,5-bis(methyloxy)anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Produkt 1

HCID 594526443-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2,5-bis(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamideAusbeute 40,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidKatalysatorHCID 887MethanolLösungsmittelHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

In a 5 mL microwave vial with septum cap, 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (0.200 g, 0.433 mmol), 4-(1,4′-bipiperidin-1′-yl)-2,5-bis(methyloxy)aniline (0.166 g, 0.520 mmol) were taken up in iPrOH (3 mL) and concentrated HCl (4 drops) was added. The vial was sealed and heated in the microwave at 180° C. for 40 min. Reaction was complete by MS, it was cooled rt, neutralized with 7N ammonia in MeOH, and concentrated in vacuo. The resulting residue was taken up in DCM and purified by column chromatography using basic alumina. The desired combined fractions were concentrated and the resulting solid was triturated with DCM and hexane, filtered and air dried to give the title compound (0.130 g, 40%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.23 (s, 1H), 9.41 (br. s., 1H), 8.50 (s, 1H), 8.33 (s, 1H), 8.24 (d, J=5.1 Hz, 1H), 8.05 (d, J=7.7 Hz, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.73 (d, J=9.2 Hz, 1H), 7.60 (t, J=7.9 Hz, 1H), 7.43-7.50 (m, 1H), 7.36-7.42 (m, 1H), 7.34 (s, 1H), 7.20 (t, J=8.1 Hz, 2H), 6.94-7.00 (m, 1H), 6.66 (s, 1H), 6.50 (d, J=5.1 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.43 (d, J=11.7 Hz, 2H), 2.51-2.58 (m, 2H), 2.26-2.35 (m, 1H), 1.77 (d, J=13.6 Hz, 2H), 1.53-1.64 (m, 2H), 1.48 (s, 4H), 1.38 (s, 2H). MS (M+H, ES+) 745.

Aufarbeitung

  1. customIn a 5 mL microwave vial with septum cap
  2. customThe vial was sealed
  3. customReaction
  4. temperaturewas cooled rt
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography
  7. concentrationwere concentrated
  8. customthe resulting solid was triturated with DCM and hexane
  9. filtrationfiltered
  10. customair dried

Quellen und Nachweise

ORD-Eintrag
ord-17191fd4eeb9499388f44cb71ecaf448
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093239B2

Notizen zur Reaktion

Wird geladen…