Ammonia → 2-((3-(4-(Azetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921821노트

반응식

HRID 921821 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)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=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][N:38]([CH:41]2[CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42]2)[CH2:37][CH2:36]1.N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.N>ClCCl>[NH:43]1[CH2:44][CH:41]([N:38]2[CH2:39][CH2:40][N:35]([C:3]3[C:2]([Cl:1])=[C:7]([NH:8][C:9]4[N:14]=[C:13]([N:15]([CH:25]5[CH2:26][CH2:27]5)[CH2:16][C:17]5[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=5)[C:12]5=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]5[N:10]=4)[CH:6]=[C:5]([C:33]#[N:34])[CH:4]=3)[CH2:36][CH2:37]2)[CH2:42]1

참가 물질

6

반응물 4

HCID 222AmmoniaHCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 89924048Tert-butyl 3-(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)piperazin-1-yl)azetidine-1-carboxylate

생성물 1

HCID 899231462-((3-(4-(Azetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile수율 72.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of tert-butyl 3-(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)piperazin-1-yl)azetidine-1-carboxylate (400 mg, 0.563 mmol) in dichloromethane (4.0 mL) at 0° C., was added 2,6-lutidine (0.197 mL, 1.690 mmol). After that TMS-OTf (0.305 mL, 1.690 mmol) was added drop wise. The reaction mixture was allowed to warm to room temperature and stirred for 5 h. The reaction mixture was diluted with dichloromethane (50 mL) and poured into a separating funnel containing liquor ammonia (5 mL). The aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic layer were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was washed with pentane (3×10 ml) and diethyl ether (3×5 mL). After the washing the resultant solid was dried under vacuum to get 2-((3-(4-(azetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (250 mg) as a off white solid.

후처리

  1. additionpoured into a separating funnel
  2. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
  3. washThe combined organic layer were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washThe crude material was washed with pentane (3×10 ml) and diethyl ether (3×5 mL)
  8. customAfter the washing the resultant solid was dried under vacuum

출처 및 근거

ORD 기록
ord-ae605cdd134842929d7c06aaa5368b9e
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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