Cesium carbonate → (+/-) Tert-butyl(2-((2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate

HRID 921697노트

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HRID 921697 반응식
[CH:1]1([N:4](CC2C=CC(OC)=CC=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]([CH:35]=[C:36]([N:39]2[CH2:44][CH2:43][N:42]([CH:45]3[CH2:48][O:47][CH2:46]3)[CH:41]([C:49]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[O:50])[CH2:40]2)[C:37]=1[Cl:38])[C:33]#[N:34].[CH3:57][C:58]1(C)[C:84]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:59]1=2.[C:99](=[O:102])([O-])[O-:100].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].O1CCOCC1>[Cl:38][C:37]1[C:36]([N:39]2[CH2:44][CH2:43][N:42]([CH:45]3[CH2:48][O:47][CH2:46]3)[CH:41]([C:49]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[O:50])[CH2:40]2)=[CH:35][C:32]([C:33]#[N:34])=[CH:31][C:30]=1[NH:29][C:7]1[N:6]=[C:5]([N:4]([CH:1]2[CH2:3][CH2:2]2)[C:99](=[O:102])[O:100][C:58]([CH3:84])([CH3:59])[CH3:57])[C:10]2=[N:11][CH:12]=[C:13]([C:14]#[N:15])[N:9]2[N:8]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86708519HCID 86708519, 화합물2회HCID 867085723-Amino-4-chloro-5-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)benzonitrile

생성물 1

HCID 86708573(+/-) Tert-butyl(2-((2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate수율 71%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

(+/−) Tert-butyl (2-chloro-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate (Intermediate 1)(30 mg, 0.090 mmol), 3-amino-4-chloro-5-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)benzonitrile (36.4 mg, 0.090 mmol), palladium (II) acetate (6.04 mg, 0.027 mmol), dppf (4.97 mg, 8.96 μmol), Xantphos (5.19 mg, 8.96 mol), and cesium carbonate (52.6 mg, 0.161 mmol) were combined in a 10 ml flask and Dioxane (1 mL) was added. The flask was evacuated and backfilled with N2 3×, then heated at 100° C. for 1 h. The reaction was cooled to room temperature and filtered through celite, rinsing with EtOAc. The solvent was removed in vacuo and the crude material was purified by flash column (0-5% MeOH/DCM). (+/−) Tert-butyl (2-((2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate (45 mg) was obtained as a yellow glass.

후처리

  1. customThe flask was evacuated
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through celite
  4. washrinsing with EtOAc
  5. customThe solvent was removed in vacuo
  6. customthe crude material was purified by flash column (0-5% MeOH/DCM)

출처 및 근거

ORD 기록
ord-7aad47e2919d4deaa5223f0f408ad357
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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