Diethylamine → tert-Butyl N-[(3S)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-2-oxo-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate

HRID 626905ノート

反応式

HRID 626905 の反応式
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:18])=[C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12](I)[N:11]=2)[CH:9]=1)[CH3:2].[O:19]=[C:20]1[C@@:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH2:26][C:27]#[CH:28])[CH2:24][CH2:23][CH2:22][N:21]1[CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42].N(CC)CC>C1COCC1.CCOC(C)=O.CCCC(C)C.[Cu](I)I>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:18])=[C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]([C:28]#[C:27][CH2:26][C@@:25]3([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:24][CH2:23][CH2:22][N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:43])([CH3:42])[CH3:44])[C:20]3=[O:19])[N:11]=2)[CH:9]=1)[CH3:2]

参加物

7

反応物 3

HCID 8021DiethylamineHCID 900151884-(5-Ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidineHCID 90016171tert-Butyl N-[(3S)-2-oxo-3-prop-2-ynyl-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate

生成物 1

HCID 90016260tert-Butyl N-[(3S)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-2-oxo-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate収率 71.4%

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 8028Tetrahydrofuran溶媒HCID 21882781Isohexane ethyl acetate溶媒

反応条件

温度
20 °C

実験手順

Copper iodide (17.27 mg, 0.09 mmol), followed by PdCl2(Ph3P)2 (31.83 mg, 0.05 mmol) was added portionwise to a solution of 4-(5-ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidine (which may be prepared as described in Description 17) (389.81 mg, 1.09 mmol), tert-butyl N-[(3S)-2-oxo-3-prop-2-ynyl-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate (which may be prepared as described in D25) (347 mg, 0.9100 mmol) and Et2NH (0.47 mL, 4.54 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 90 hrs. The solvent was evaporated and the residue was purified using a Biotage SP4 with a 25 g SNAP cartridge, eluting with 0 to 50% EtOAc/i-hexane affording the tert-butyl N-[(3S)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-2-oxo-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate (D26) (397 mg, 0.6478 mmol, 71.4% yield) as a dark yellow oil.

後処理

  1. customThe solvent was evaporated
  2. customthe residue was purified

出典と根拠

ORDレコード
ord-f462cfdfce894280be1218790fdb2aae
出典データセット
uspto-grants-2016_04
特許番号
US09309254B2

反応ノート

読み込み中…