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Propylamine → 2-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-ethynyl-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1858101
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HRID 1858101 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24](I)[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[C:32]([CH3:37])[CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:38](N)[CH2:39]C.C[Si](C#C)(C)C>C(OCC)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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:28])=[C:24]([C:38]#[CH:39])[CH:25]=2)[NH:20][C:19](=[O:29])[C:18]=1[C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[C:32]([CH3:37])[CH:31]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

7

반응물 3

HCID 7852PropylamineHCID 66111TrimethylsilylacetyleneHCID 539972552-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-iodo-2-oxo-1,2-dihydro-quinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 544333822-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-ethynyl-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 3

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
촉매
HCID 178418397HCID 178418397, 화합물촉매
HCID 3283Diethyl Ether용매

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온도
95 °C

실험 절차

To a suspension of 2-{2-[7-chloro-3-(3,5-dimethylphenyl)-6-iodo-2-oxo- 1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (EXAMPLE 4.2 Step B, 200 mg in 3 mL N,N-dimethylformamide) was added tetrakis(triphenylphosphine)palladium (18 mg) followed by copper(I) iodide (30 mg), n-propylamine (0.26 mL) and trimethylsilylacetylene (0.45 mL) and the mixture sealed in a thick-walled tube. This was heated to 95° C. on an oil bath for 10 hours, then cooled to room temperature and diluted with diethyl ether. This was washed successively with water and brine and the combined organics dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane, 30:70; then 40:60) gave a mixture of the title compound and the corresponding trimethylsilyl derivative (155 mg). This material was converted to the title compound by treatment with 4.4 mg of potassium carbonate in 2 mL methanol. After 1 hour, the mixture was diluted with methylene chloride, washed with half-saturated sodium chloride, then brine and dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane, 30:70; then 40:60) gave the title compound (127 mg).

후처리

  1. customthe mixture sealed in a thick-walled tube
  2. temperaturecooled to room temperature
  3. washThis was washed successively with water and brine
  4. dry with materialthe combined organics dried over magnesium sulfate
  5. customPurification of the
  6. concentrationconcentrate by flash chromatography on silica gel (ethyl acetate
  7. customthen 40:60) gave

출처 및 근거

ORD 기록
ord-ed2116e08e1e454cabaff4d0a715c71f
출처 데이터셋
uspto-grants-2000_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06150352

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