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 921750ノート

反応式

HRID 921750 の反応式
[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]

参加物

5

反応物 3

HCID 10796Cesium carbonate2 回HCID 86708519HCID 86708519、化合物3 回HCID 86708633Methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate

生成物 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)carbamate収率 179.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
45 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5614862ca2d048b09f73879bab587a07
出典データセット
uspto-grants-2016_03
特許番号
US09273057B2

反応ノート

読み込み中…