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Triethylamine → (S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

HRID 1042650
ノート
印刷プレビュー

反応式

HRID 1042650 の反応式
[F:1][C:2]1[CH:35]=[CH:34][C:33](I)=[CH:32][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=1[N:17]1[CH2:22][CH2:21][CH2:20][C@H:19]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:18]1)=[O:5].[C:37]([C:39]1[CH:40]=[N:41][C:42]([NH2:45])=[N:43][CH:44]=1)#[CH:38].C(N(CC)CC)C>CC#N.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:45][C:42]1[N:43]=[CH:44][C:39]([C:37]#[C:38][C:33]2[CH:34]=[CH:35][C:2]([F:1])=[C:3]([CH:32]=2)[C:4]([NH:6][C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=2[N:17]2[CH2:22][CH2:21][CH2:20][C@H:19]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:18]2)=[O:5])=[CH:40][N:41]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 8471TriethylamineHCID 161090215-Ethynylpyrimidin-2-amineHCID 16109029(S)-tert-butyl 1-(2-(2-fluoro-5-iodobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

生成物 1

HCID 16109030(S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

試薬・触媒・溶媒 3

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
触媒
HCID 178418476HCID 178418476、化合物触媒
HCID 6342Acetonitrile溶媒

実験手順

In a 25-mL RBF (S)-tert-butyl 1-(2-(2-fluoro-5-iodobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate (0.496 g, 0.80 mmol), 5-ethynylpyrimidin-2-amine (0.19 g, 1.6 mmol), Bis(triphenylphosphine)palladium(II) dichloride (0.028 g, 0.040 mmol), and Copper(I) iodide (0.0076 g, 0.040 mmol) were taken up in CH3CN and Triethylamine (1.7 ml, 12 mmol) was added, and the tube was flushed with nitrogen. The tube was sealed and the reaction heated to 70 deg. C for 16 h. The reaction was cooled and transferred to a larger flask with EtOAc and concentrated in vacuo. The solid was adsorbed onto 4 g silica gel from 10% MeOH/MC purified by Isco {Redi-Sep® pre-packed silica gel column (80 g); eluent 0-75% EtOAc/hexanes over 30 min}. Product-containing fractions were concentrated to afford (S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate as a orange foam. MS m/z=613 [M+H]+. Calc'd for C31H32F4N6O3: 612.

後処理

  1. customthe tube was flushed with nitrogen
  2. customThe tube was sealed
  3. temperaturethe reaction heated to 70 deg. C for 16 h
  4. temperatureThe reaction was cooled
  5. customtransferred to a larger flask with EtOAc
  6. concentrationconcentrated in vacuo
  7. custompurified by Isco {Redi-Sep® pre-packed silica gel column (80 g)
  8. concentrationProduct-containing fractions were concentrated

出典と根拠

ORDレコード
ord-9859d3ae80e94334b3b05845c1616f44
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08557996B2

反応ノート

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