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 1430930노트

반응식

HRID 1430930 반응식
[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]

참가 물질

5

반응물 3

HCID 10796Cesium carbonate2회HCID 86708519HCID 86708519, 화합물3회HCID 86708633Methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate

생성물 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)carbamate수율 179.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
45 °C

실험 절차

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 dilute 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.

후처리

  1. customThe mixture was partitioned between EtOAc and dilute aq. NH4Cl solution
  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

출처 및 근거

ORD 기록
ord-d121735f5ae84cad8999d12505239313
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940736B2

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