Trifluoroacetic acid → HCID 89922461, 화합물

HRID 921918노트

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HRID 921918 반응식
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)CC3C=CC(OC)=CC=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][O:38][CH:37]([CH2:41][N:42](CC2C=CC(OC)=CC=2)[S:43]([CH3:46])(=[O:45])=[O:44])[CH2:36]1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH:25]3[CH2:26][CH2:27]3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][O:38][CH:37]([CH2:41][NH:42][S:43]([CH3:46])(=[O:45])=[O:44])[CH2:36]1

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 89923300(+/-)-N-((4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)morpholin-2-yl)methyl)-N-(4-methoxybenzyl)methanesulfonamide

생성물 1

HCID 89922461HCID 89922461, 화합물수율 13.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a round bottom flask charged with (+/−)-N-((4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)morpholin-2-yl)methyl)-N-(4-methoxybenzyl)methanesulfonamide (43.1 mg, 0.055 mmol) in dichloromethane (220 μl) was added anisole (30.0 μl, 0.275 mmol), followed by trifluoroacetic acid (169 μl, 2.200 mmol). The reaction mixture was stirred at room temperature ON. Excess TFA was removed by concentration in vacuo. The crude residue was taken up in methanol and free based on a 1 g Phenomenex Strata SCX column. The column was flushed with 3 column volumes MeOH and 1 column volume 7 N NH3/MeOH. The ammonia containing fraction was concentrated in vacuo. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10-mM ammonium acetate; Gradient: 10-100% B over 15 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. (+/−)-N-((4-(2-Chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)morpholin-2-yl)methyl)methanesulfonamide (3.9 mg) was isolated.

후처리

  1. customExcess TFA was removed by concentration in vacuo
  2. customThe column was flushed with 3 column volumes MeOH and 1 column volume 7 N NH3/MeOH
  3. concentrationThe ammonia containing fraction was concentrated in vacuo
  4. customThe crude material was purified via preparative LC/MS with the following conditions
  5. customa 5-minute hold
  6. additionFractions containing the desired product
  7. customdried via centrifugal evaporation

출처 및 근거

ORD 기록
ord-bffbe7050a5b430294eb07a513450bba
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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