1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-((2-Chloro-5-cyano-3-(1-(3-(2-hydroxyethyl)oxetan-3-yl)piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430919노트

반응식

HRID 1430919 반응식
[Cl:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:6][C:5]([C:14]#[N:15])=[CH:4][C:3]=1[NH:16][C:17]1[N:22]=[C:21]([N:23]([CH:33]2[CH2:35][CH2:34]2)[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:20]2=[N:36][CH:37]=[C:38]([C:39]#[N:40])[N:19]2[N:18]=1.N12CCCN=C1CCCCC2.[O:52]1[CH2:55][C:54](=[CH:56][CH:57]=[O:58])[CH2:53]1.[BH4-].[Na+]>C1COCC1.CCOC(C)=O.CO>[Cl:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][N:11]([C:54]3([CH2:56][CH2:57][OH:58])[CH2:55][O:52][CH2:53]3)[CH2:10][CH2:9]2)=[CH:6][C:5]([C:14]#[N:15])=[CH:4][C:3]=1[NH:16][C:17]1[N:22]=[C:21]([N:23]([CH:33]2[CH2:35][CH2:34]2)[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:20]2=[N:36][CH:37]=[C:38]([C:39]#[N:40])[N:19]2[N:18]=1

참가 물질

8

반응물 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 4311764Sodium borohydrideHCID 533084702-(Oxetan-3-ylidene)acetaldehydeHCID 867085292-((2-Chloro-5-cyano-3-(piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

생성물 1

HCID 867086242-((2-Chloro-5-cyano-3-(1-(3-(2-hydroxyethyl)oxetan-3-yl)piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile수율 49.3%

시약·촉매·용매 3

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
-15 °C

실험 절차

To a solution of 2-((2-chloro-5-cyano-3-(piperidin-4-yl)phenyl)amino)-4-(cyclopropyl (4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (375D) (50 mg, 0.090 mmol) in dry THF (0.3 mL) was added 1,8-Diazabicyclo[5.4.0]undec-7-ene (diluted with THF, 10V %) (0.013 mL, 9.02 μmol) at RT. The mixture was cooled in an ice/NaCl bath (−15° C.). To this was added 2-(oxetan-3-ylidene)acetaldehyde (36 mg, 0.367 mmol), and left stirring at −15° C. to 0° C. for 2.5 h, then the mixture was put in the freezer for 7 days. To the reaction mixture was added MeOH (1 mL), then sodium borohydride (10.30 mg, 0.271 mmol) at RT and stirred for 2 hrs. Diluted with EtOAc, washed with NaHCO3, water, brine, and dried over Na2SO4. Removal of the solvent. The crude material was purified by radial chromatography, eluting with DCM containing 0 to 1% MeOH to give 2-((2-chloro-5-cyano-3-(1-(3-(2-hydroxyethyl)oxetan-3-yl)piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (29 mg).

후처리

  1. waitleft
  2. waitthe mixture was put in the freezer for 7 days
  3. washwashed with NaHCO3, water, brine
  4. dry with materialdried over Na2SO4
  5. customRemoval of the solvent
  6. customThe crude material was purified by radial chromatography
  7. washeluting with DCM containing 0 to 1% MeOH

출처 및 근거

ORD 기록
ord-dd6ef608372d4ab387c931e3baa16714
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940736B2

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