Triethylamine → HCID 178471562、化合物

HRID 22023

反応式

HRID 22023 の反応式
[OH:1][C:2]1[C:3]2[C:17]([C:18]#[CH:19])=[CH:16][NH:15][C:4]=2[N:5]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[N:7]=1.[CH2:20]([O:22][C:23](=[O:42])[C@H:24]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[NH:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][C:30](I)=[CH:29][CH:28]=1)[CH3:21].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C.[Pd](Cl)Cl.O>[CH2:20]([O:22][C:23](=[O:42])[C@H:24]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[NH:25][C:26](=[O:34])[C:27]1[CH:28]=[CH:29][C:30]([C:19]#[C:18][C:17]2[C:3]3[C:2]([OH:1])=[N:7][C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:5][C:4]=3[NH:15][CH:16]=2)=[CH:31][CH:32]=1)[CH3:21]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 1885228diethyl (2S)-2-[(4-iodobenzoyl)amino]pentanedioateHCID 178437174HCID 178437174、化合物

生成物 1

HCID 178471562HCID 178471562、化合物収率 85%

試薬・触媒・溶媒 3

HCID 24290Palladium Chloride触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒2 回

実験手順

To a suspension of 3.33 g (12.9 mmol) of N-(4-hydroxy-5-ethynyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropionamide in 64 mL of acetonitrile stirred under nitrogen was added 5.77 g (28.4 mmol) of BSA and the resulting mixture was stirred at 40° C. for 2 hours, then cooled to ambient temperature. To the resulting solution was added sequentially 5.58 g (12.9 mmol) of N-4-iodobenzoyl-L-glutamic acid diethyl ester, 2.6 g (25.8 mmol) of triethylamine, and a mixture of 0.114 g (0.65 mmol) of palladium(II) chloride and 0.338 g (1.29 mmol) of triphenylphosphine in 16 mL of acetonitrile. The resulting mixture was heated under reflux overnight (18 hours), after which time HPLC analysis of an aliquot indicated complete conversion of the (acetylenic) starting material. The mixture was cooled to ambient temperature and 2 mL of water was added. The resulting suspension was stirred for 30 minutes, filtered, and the precipitate washed with acetonitrile and dried, affording 6.15 g (85%) of N-[4-[2-[2-(2,2-dimethylpropionyl)amino-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl ]ethynyl]benzoyl]-L-glutamic acid diethyl ester as a tan solid. The melting point and NMR spectral data for the product were in agreement with data obtained on an authentic sample prepared by the procedure of Example 3.

後処理

  1. additionwas added 5.77 g (28.4 mmol) of BSA
  2. stirringthe resulting mixture was stirred at 40° C. for 2 hours
  3. temperatureThe resulting mixture was heated
  4. temperatureunder reflux overnight (18 hours)
  5. temperatureThe mixture was cooled to ambient temperature
  6. stirringThe resulting suspension was stirred for 30 minutes
  7. filtrationfiltered
  8. washthe precipitate washed with acetonitrile
  9. customdried

出典と根拠

ORDレコード
ord-284b254b09ae4d3e9cdfeff64dbfd8a2
出典データセット
uspto-grants-1995_06
特許番号
US05426187

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