Ammonia → 4-(1-methylpiperidin-4-yloxy)-2-phenylethynyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

HRID 1773869노트

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HRID 1773869 반응식
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[CH:3]=1.[C:24]1([C:30]#[CH:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCN(CC)CC.N>C(#N)C.[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.O>[CH3:19][N:16]1[CH2:17][CH2:18][CH:13]([O:12][CH:9]2[C:8]3[CH:20]=[CH:21][CH:22]=[CH:23][C:7]=3[CH2:6][CH2:5][N:4]3[C:10]2=[N:11][CH:2]=[C:3]3[C:31]#[C:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:14][CH2:15]1

참가 물질

9

반응물 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 726957782-iodo-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

생성물 1

HCID 867039564-(1-methylpiperidin-4-yloxy)-2-phenylethynyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
80 °C

실험 절차

To a solution of compound 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (100 mg, 0.24 mmoles) in ACN (600 μL) in a screw-capped vial under argon are added CuI (9 mg, 0.048 mmole), Pd(PPh3)4 (28 mg, 24 μmoles), phenylacetylene (109 μL, 0.96 mmole) and NEt3 (600 μL). The reaction mixture is heated at 80° C. overnight. Water is added and pH adjusted to 9-10 with concentrated aqueous ammonia solution. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (98:2:0.2) to (95:5:0.5) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-(1-methylpiperidin-4-yloxy)-2-phenylethynyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

후처리

  1. extractionThe aqueous phase is extracted three times with CH2Cl2
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is pre-purified by silica gel chromatography
  6. washeluting with (CH2Cl2:MeOH:NH4OH) (9:1:1)

출처 및 근거

ORD 기록
ord-3dd9ba2d029240bc8e28b60dae68644e
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255101B2

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