1-(2-Methylbut-3-yn-2-yl)piperidine → N-(3-fluoro-4-(2-(3-methyl-3-(piperidin-1-yl)but-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676308Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676308
[F:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH3:35][C:36]([N:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1)([C:38]#[CH:39])[CH3:37]>>[F:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:39]#[C:38][C:36]([CH3:37])([N:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)[CH3:35])[S:17][C:10]=12

Komponenten

3

Edukt 2

HCID 2425101-(2-Methylbut-3-yn-2-yl)piperidineHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Produkt 1

HCID 67348672N-(3-fluoro-4-(2-(3-methyl-3-(piperidin-1-yl)but-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideAusbeute 38,5 %

Versuchsvorschrift

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 20 mg, 0.0338 mmol) and 1-(2-methylbut-3-yn-2-yl)piperidine (10.2 mg, 0.0676 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.34) eluting with 10% MeOH/DCM. A second purification by preparative TLC was conducted (0.5 mm thickness, Rf=0.49), eluting with 15% MeOH in EtOAc, in order to obtain product of adequate purity. The product was obtained as a beige powder (8 mg, 38%). HPLC: 98% purity (254 nm); LCMS (APCI−): 100% purity, 220 nm, m/z 613 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.48 (d, J=6 Hz, 1H), 8.15 (s, 1H), 7.74 (m, 1H), 7.55 (s, 1H), 7.45 (m, 2H), 7.24 (m, 2H), 7.07 (t, J=9 Hz, 2H), 6.50 (d, J=6 Hz, 1H), 2.66 (br s, 4H), 1.81 (m, 2H), 1.64 (m, 6H), 1.51 (m, 8H).

Aufarbeitung

  1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.34)
  2. washeluting with 10% MeOH/DCM
  3. customA second purification by preparative TLC
  4. washeluting with 15% MeOH in EtOAc, in order
  5. customto obtain product of adequate purity

Quellen und Nachweise

ORD-Eintrag
ord-6336f240dbbd46bab1f1dd4a4b5baeda
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003662B2

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