Nitrogen → N-(4-[{4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-4-methyl-3-[(2-oxo-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-6-yl)ethynyl]benzamide

HRID 1255953ノート

反応式

HRID 1255953 の反応式
[CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:30])[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([C:28]#[CH:29])[CH:22]=3)=[CH:15][C:14]=2[C:31]([F:34])([F:33])[F:32])[CH2:8][CH2:7]1)([CH3:4])=[O:3].Br[C:36]1[CH:45]=[N:44][C:43]2[NH:42][C:41](=[O:46])CO[C:38]=2[CH:37]=1.N#N.C(N(CC)C(C)C)(C)C.C[CH2:59][O:60]C(C)=O>[Cu]I.O.CN(C=O)C>[CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:30])[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([C:28]#[C:29][C:36]4[CH:45]=[N:44][C:43]5[NH:42][C:41](=[O:46])[O:60][CH2:59][C:38]=5[CH:37]=4)[CH:22]=3)=[CH:15][C:14]=2[C:31]([F:34])([F:32])[F:33])[CH2:8][CH2:7]1)([CH3:4])=[O:3]

参加物

9

反応物 5

HCID 947NitrogenHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 159259837-bromo-2H,3H,4H-pyrido(3,2-b)(1,4)oxazin-3-oneHCID 86632313N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-3-ethynyl-4-methylbenzamide

生成物 1

HCID 68911400N-(4-[{4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-4-methyl-3-[(2-oxo-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-6-yl)ethynyl]benzamide

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-3-ethynyl-4-methylbenzamide (0.22 mmol), 7-bromo-4H-pyrido[3,2-b][1,4]oxazin-3-one (45.8 mg, 0.2 mmol), Pd[(PPh3)]4 (11.6 mg, 0.01 mmol). CuI (2.9 mg, 0.015 mmol) is placed in a vial capped with rubber septa. This vial is subjected to 3 cycles of vacuum-refilling with N2. To this mixture is added anhydrous N,N-diisopropylethylamine (0.1 mL, 0.6 mmol) and DMF (1.0 mL). The resulting solution is stirred at 80° C. for 24 h. After the reaction mixture is cooled, water and EtOAc are added to facilitate the extraction. The combined organic layers are dried over Na2SO4, filtered, and then concentrated on a rotavap and the residue is purified on a silica gel column (eluent: 10% MeOH in CH2Cl2, MeOH is pre-saturated with NH3 gas).

後処理

  1. customa vial capped with rubber septa
  2. temperatureAfter the reaction mixture is cooled
  3. extractionthe extraction
  4. dry with materialThe combined organic layers are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated on a rotavap
  7. customthe residue is purified on a silica gel column (eluent: 10% MeOH in CH2Cl2, MeOH is pre-saturated with NH3 gas)

出典と根拠

ORDレコード
ord-a0798ba5100a4f8f80f6d01bdd75d486
出典データセット
uspto-grants-2013_06
特許番号
US08461167B2

反応ノート

読み込み中…