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Hydrochloric Acid → 5-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide

HRID 419583
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 419583
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]3=[N:10][C:9]=2[C:18]2[CH:19]=[CH:20][C:21]([O:35][CH3:36])=[C:22]([CH:34]=2)[C:23]([NH:25][C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=2[F:33])=[O:24])[CH:5]=[CH:4][N:3]=1.[N:37]1([CH:43]2[CH2:48][CH2:47][N:46]([C:49]3[CH:55]=[CH:54][C:52]([NH2:53])=[C:51]([O:56][CH3:57])[CH:50]=3)[CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.Cl.O1CCOCC1.C[O-].[Na+]>FC(F)(F)CO.CO.C(Cl)Cl.CCCCCC>[N:37]1([CH:43]2[CH2:48][CH2:47][N:46]([C:49]3[CH:55]=[CH:54][C:52]([NH:53][C:2]4[N:7]=[C:6]([C:8]5[N:12]6[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]6=[N:10][C:9]=5[C:18]5[CH:19]=[CH:20][C:21]([O:35][CH3:36])=[C:22]([CH:34]=5)[C:23]([NH:25][C:26]5[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=5[F:33])=[O:24])[CH:5]=[CH:4][N:3]=4)=[C:51]([O:56][CH3:57])[CH:50]=3)[CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 10942334Sodium MethoxideHCID 594529085-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamideHCID 597120872-Methoxy-4-[4-(1-piperidyl)-1-piperidyl]aniline

Produkt 1

HCID 59452936
5-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide
Ausbeute 86,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 64092,2,2-TrifluoroethanolLösungsmittelHCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To 5-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)-2-(methyloxy)benzamide (Example 197, step A) (114 mg, 0.22 mmol) and 4-(1,4′-bipiperidin-1′-yl)-2-(methyloxy)aniline (Example 22, step C) (65 mg, 0.22 mmol) in 2,2,2-trifluoroethanol (1.5 mL) was added 4 M HCl in dioxane (112 μL, 0.45 mmol). The mixture was stirred and heated on a microwave at 150° C. for 45 min, then cooled to rt. The mixture was neutralized with 0.5M sodium methoxide in MeOH. The mixture was concentrated under vacuum and the residue purified by silica gel chromatography to give a yellow oil. The oil was dissolved in minimal DCM, then hexane was added until a precipitate was formed. The slurry was cooled at −10° C. for 30 min, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (147 mg, 0.19 mmol, 86%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.79 (s, 1H), 9.44 (br s, 1H), 8.49 (s, 1H), 8.20 (d, 1H, J=5.32 Hz), 8.09 (d, 1H, J=2.02 Hz), 7.75-7.79 (m, 1H), 7.58 (dd, 1H, J=2.66, 9.62 Hz), 7.35-7.43 (m, 2H), 7.29 (d, 1H, J=8.80 Hz), 7.19 (t, 2H, J=8.06 Hz), 6.98-7.04 (m, 1H), 6.68 (d, 1H, J=2.20 Hz), 6.48-6.53 (m, 2H), 3.99 (s, 3H), 3.70-3.81 (m, 5H), 2.61-2.69 (m, 2H), 2.41-2.48 (m, 4H), 2.29-2.37 (m, 1H), 1.76-1.83 (m, 2H), 1.44-1.60 (m, 6H), 1.34-1.41 (m, 2H). MS (ESI): 763 [M+H]+.

Aufarbeitung

  1. temperaturecooled to rt
  2. concentrationThe mixture was concentrated under vacuum
  3. customthe residue purified by silica gel chromatography
  4. customto give a yellow oil
  5. customwas formed
  6. temperatureThe slurry was cooled at −10° C. for 30 min
  7. filtrationfilter
  8. washwashing the solids with cold hexanes
  9. customThe solids were dried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ce8b803311a34913a6a0967ed6d3a23a
Quelldatensatz
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08093239B2

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