Acetonitrile → 4-(3,3-dimethylbut-1-ynyl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

HRID 1042806ノート

反応式

HRID 1042806 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][N:28]=4)[N:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[N:4][N:3]=1.[CH3:32][C:33]([CH3:37])([CH3:36])[C:34]#[CH:35].C(#N)C>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:32][C:33]([CH3:37])([CH3:36])[C:34]#[C:35][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][N:28]=4)[N:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[N:4][N:3]=1

参加物

7

反応物 3

HCID 6342AcetonitrileHCID 135123,3-Dimethyl-1-butyneHCID 866286654-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

生成物 1

HCID 673166724-(3,3-dimethylbut-1-ynyl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

A resealable pressure bottle, purged with argon, was charged with 4-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine (120 mg, 0.28 mmol), bis(triphenylphosphine)palladium(ii) chloride (24 mg, 0.03 mmol), copper(I) iodide (6.4 mg, 0.03 mmol), 3,3-dimethyl-1-butyne (86 μA, 0.70 mmol), and ACN (2.8 mL, 0.1 M). To the mixture was added TEA (0.785 mL, 5.6 mmol). The reaction vessel was sealed and the mixture was heated to 90° C. for 16 h. The reaction mixture was cooled to RT, diluted with DCM and filtered over Celite. The filtrate was concentrated under reduced pressure to give a brown residue, which was purified by Gilson HPLC {5-65% (0.1% TFA in CH3CN) in H2O over 20 min}. The product-containing fractions were combined, basified by addition of aq. NaHCO3 and extracted with DCM. The organic portion was dried with Na2SO4, filtered, and concentrated to afford pure 4-(3,3-dimethylbut-1-ynyl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine MS [M+H]=476.1 Calc'd for C29H25N5O2: 475.5.

後処理

  1. customA resealable pressure bottle, purged with argon
  2. customThe reaction vessel was sealed
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationfiltered over Celite
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto give a brown residue, which
  7. customwas purified by Gilson HPLC {5-65% (0.1% TFA in CH3CN) in H2O over 20 min}
  8. additionbasified by addition of aq. NaHCO3
  9. extractionextracted with DCM
  10. dry with materialThe organic portion was dried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-d6abe6393043486e94d66d22d9e7ff3e
出典データセット
uspto-grants-2013_10
特許番号
US08557816B2

反応ノート

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