Triethylamine → 4-[[4-[4-[3-[2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]-2,6-dimethyl-phenoxy]pyrimidin-2-yl]amino]benzonitrile

HRID 1893145ノート

反応式

HRID 1893145 の反応式
I[C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:8]=2)=[C:4]([CH3:25])[CH:3]=1.[CH2:26]([O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][OH:41])[C:27]#[CH:28].C(N(CC)CC)C>CN(C=O)C.C1COCC1.C(Cl)Cl.CO.[Cu]I.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>[OH:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][O:32][CH2:31][CH2:30][O:29][CH2:26][C:27]#[C:28][C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:8]=2)=[C:4]([CH3:25])[CH:3]=1

参加物

9

反応物 3

HCID 8471TriethylamineHCID 159170603,6,9,12-Tetraoxapentadec-14-yn-1-olHCID 585605744-[4-(4-Iodo-2,6-dimethylphenoxy)pyrimidin-2-ylamino]benzonitrile

生成物 1

HCID 585605804-[[4-[4-[3-[2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]-2,6-dimethyl-phenoxy]pyrimidin-2-yl]amino]benzonitrile収率 85.4%

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 21226129Dichloromethane methanol溶媒2 回

実験手順

To a deoxygenated solution of iodopyrimidine 3 (494 mg, 1.12 mmol) and 2-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethoxy)ethanol (Veciani, et al., Ibid.) (780 mg, 3.36 mmol) in dry DMF (1.5 mL) and dry THF (3.0 mL) were added successively dry triethylamine (562.0 mg, 5.55 mmol, 0.80 mL), copper (1) iodide (105.7 mg, 0.56 mmol), and tetrakis(triphenylphosphine)palladium (0) (128.3 mg, 0.11 mmol). The reaction mixture was stirred at 25° C. under a nitrogen atmosphere for 3 hours after which TLC (DCM/methanol=3:97) revealed a more polar product and consumption of starting material 3. The mixture was poured into EDTA solution (20 mL, 5%) and the organic product extracted into EtOAc (3×50 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and the solvent evaporated in vacuo to furnish a residue that was subjected to silica-gel column chromatography using DCM/MeOH (95:5) as eluent to produce 4 as a light-brown oil (522.0 mg, 0.956 mmol, 85%).

後処理

  1. customa more polar product and consumption of starting material 3
  2. additionThe mixture was poured into EDTA solution (20 mL, 5%)
  3. extractionthe organic product extracted into EtOAc (3×50 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customthe solvent evaporated in vacuo
  7. customto furnish a residue that

出典と根拠

ORDレコード
ord-aae2c27c736c4215939ec13b1d6033ba
出典データセット
uspto-grants-2013_08
特許番号
US08513205B2

反応ノート

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