Triethylamine → HCID 178500478, 화합물

HRID 477867노트

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HRID 477867 반응식
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:20][C:21]1[CH:40]=[C:39](I)[CH:38]=[CH:37][C:22]=1[C:23]([NH:25][C@H:26]([C:33]([O:35][CH3:36])=[O:34])[CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[O:24].[C:42]([NH:48][C:49]1[N:50]=[C:51]([OH:61])[C:52]2[CH:58]=[C:57]([C:59]#[CH:60])[CH:56]=[N:55][C:53]=2[N:54]=1)(=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44].C(N(CC)CC)C>C(#N)C.[Pd](Cl)Cl.[Cu](I)I>[F:20][C:21]1[CH:40]=[C:39]([C:60]#[C:59][C:57]2[CH:56]=[N:55][C:53]3[N:54]=[C:49]([NH:48][C:42](=[O:47])[C:43]([CH3:46])([CH3:44])[CH3:45])[N:50]=[C:51]([OH:61])[C:52]=3[CH:58]=2)[CH:38]=[CH:37][C:22]=1[C:23]([NH:25][C@H:26]([C:33]([O:35][CH3:36])=[O:34])[CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[O:24]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 14720611dimethyl N-(2-fluoro-4-iodobenzoyl)-L-glutamateHCID 178437079HCID 178437079, 화합물

생성물 1

HCID 178500478HCID 178500478, 화합물수율 62.5%

시약·촉매·용매 3

HCID 24290Palladium Chloride촉매HCID 83717Copper iodide촉매HCID 6342Acetonitrile용매2회

실험 절차

A mixture of 0.44 g (2.56 mmol) of palladium chloride and 1.34 g (5.12 mmol) of triphenylphosphine in 200 mL of acetonitrile is stirred under nitrogen at room temperature for 30 minutes. To this mixture is added an additional 150 mL of acetonitrile, 22.09 g (52.2 mmol) of dimethyl N-(2-fluoro-4-iodobenzoyl)-L-glutamate, 13.830 g (51.2 mmol) of 2-pivaloylamino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine, 0.0244 g (1.28 mmol) of copper iodide, and 15 mL (107.5 mmol) of triethylamine. The reaction mixture is then heated at reflux for 3 hours and then cooled to room temperature, the solvent is then removed in vacuo and the crude solid chromatographed on silica gel with 1:19 methanol:methylene chloride to give 18.1 g (62.5%) of dimethyl N-(2-fluoro-4-[2-(2-pivaloylamino-4-hydroxypyrido[2,3-d]-pyrimidin-6-yl)ethynyl]-benzoyl)-L-glutamate as a white solid m.p. 204°-207° C. (dec); Rf =0.60 (1:19 methanol: chloroform), Mass (FD)=565; IR (KBr, cm-1)=813, 1151, 1201, 1270, 1375, 1444, 1481, 1490, 1527, 1548, 1598, 1623, 1649, 1670, 1741, 1753; UV (EtOH) λmax =325 (epsilon=41100), 266 (epsilon=14600), 210 (epsilon=35700).

후처리

  1. temperatureThe reaction mixture is then heated
  2. temperatureat reflux for 3 hours
  3. temperaturecooled to room temperature
  4. customthe solvent is then removed in vacuo
  5. customthe crude solid chromatographed on silica gel with 1:19 methanol

출처 및 근거

ORD 기록
ord-2b034f1739244826906b4e164bae58b0
출처 데이터셋
uspto-grants-1989_12
특허 번호
US04889859

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