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Diisopropylethylamine → (R)-N-(4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide

HRID 923220
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HRID 923220 반응식
[C:1]([C:3]1[N:7]2[N:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][CH:4]=1)#[CH:2].[CH3:12][N:13]([CH3:41])[C@@H:14]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:36])[C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[C:30](I)[CH:29]=3)=[CH:22][C:21]=2[C:37]([F:40])([F:39])[F:38])[CH2:15]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH3:41][N:13]([CH3:12])[C@@H:14]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:36])[C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[C:30]([C:2]#[C:1][C:3]4[N:7]5[N:8]=[CH:9][CH:10]=[CH:11][C:6]5=[N:5][CH:4]=4)[CH:29]=3)=[CH:22][C:21]=2[C:37]([F:40])([F:39])[F:38])[CH2:15]1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 468387603-Ethynylimidazo[1,2-b]pyridazineHCID 66735622(R)-N-(4-((3-(Dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide

생성물 1

HCID 24826797(R)-N-(4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide수율 13.1%

시약·촉매·용매 3

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
촉매
HCID 178418397HCID 178418397, 화합물촉매
HCID 6228Dimethylformamide용매

실험 절차

A mixture of 3-ethynylimidazo[1,2-b]pyridazine (0.051 g, 0.34 mmol), 0.150 g (0.28 mmol) of (R)—N-(4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide, 0.016 g (0.014 mmol) of Pd(PPh3)4, 0.004 g (0.021 mmol) of CuI, and 0.09 mL (0.51 mmol) of N,N-diisopropylethylamine in 3.5 mL of DMF was stirred at ambient temperature, under an atmosphere of N2, for 3 days (reaction pushed to completion with additional equivalents of reagents and heating to 80° C.). The reaction mixture was concentrated and the crude product was purified by silica gel chromatography (eluted with 0-10% MeOH/DCM; MeOH was pre-saturated with ammonia gas) to provide 0.020 g of product as a solid: 547 m/z (M+H).

후처리

  1. custom(reaction pushed to completion with additional equivalents of reagents and heating to 80° C.)
  2. concentrationThe reaction mixture was concentrated
  3. customthe crude product was purified by silica gel chromatography (eluted with 0-10% MeOH/DCM; MeOH was pre-saturated with ammonia gas)

출처 및 근거

ORD 기록
ord-f6d0c8980ce342168c23c1b9cef56468
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09278971B2

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