Cesium carbonate → Methyl (3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4 methoxybenzyl)carbamate

HRID 921750Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921750
[CH:1]1([N:4]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:5]2[C:10]3=[N:11][CH:12]=[C:13]([C:14]#[N:15])[N:9]3[N:8]=[C:7](S(C)(=O)=O)[N:6]=2)[CH2:3][CH2:2]1.[NH2:29][C:30]1[CH:31]=[C:32]([N:47]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=2)[C:48](=[O:51])[O:49][CH3:50])[CH:33]=[C:34]([N:37]2[CH2:42][CH2:41][N:40]([CH:43]3[CH2:46][O:45][CH2:44]3)[CH2:39][CH2:38]2)[C:35]=1[F:36].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:14]([C:13]1[N:9]2[C:10]([C:5]([N:4]([CH:1]3[CH2:3][CH2:2]3)[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[N:6][C:7]([NH:29][C:30]3[CH:31]=[C:32]([N:47]([CH2:52][C:53]4[CH:54]=[CH:55][C:56]([O:59][CH3:60])=[CH:57][CH:58]=4)[C:48](=[O:51])[O:49][CH3:50])[CH:33]=[C:34]([N:37]4[CH2:38][CH2:39][N:40]([CH:43]5[CH2:46][O:45][CH2:44]5)[CH2:41][CH2:42]4)[C:35]=3[F:36])=[N:8]2)=[N:11][CH:12]=1)#[N:15]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonate2×HCID 86708519HCID 86708519, Verbindung3×HCID 86708633Methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate

Produkt 1

HCID 86708634Methyl (3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4 methoxybenzyl)carbamateAusbeute 179,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

4-(cyclopropyl(4-methoxybenzyl)amino)-2-(methylsulfonyl)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 3) (58.4 mg, 0.146 mmol), methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (62 mg, 0.098 mmol) and Cs2CO3 (95 mg, 0.293 mmol) in DMF (1 ml) were heated at 70° C. for 80 minutes. Additional 4-(cyclopropyl(4-methoxybenzyl)amino)-2-(methylsulfonyl)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (58.4 mg, 0.146 mmol) and Cs2CO3 (95 mg, 0.293 mmol) were added and the mixture stirred at 45° C. for 16 hours. The mixture was partitioned between EtOAc and dilutes aq. NH4Cl solution. The organic layer was washed twice with dilute NaHCO3 solution, once with brine, then dried over MgSO4, filtered and evaporated to dryness to give methyl (3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4 methoxybenzyl)carbamate (134.4 mg). The material was used in the following reaction without further purification.

Aufarbeitung

  1. customThe mixture was partitioned between EtOAc
  2. washThe organic layer was washed twice with dilute NaHCO3 solution, once with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-5614862ca2d048b09f73879bab587a07
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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