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Diethylamine → tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate

HRID 626899
ノート
印刷プレビュー

反応式

HRID 626899 の反応式
[CH3:1][N:2]1[CH2:6][CH2:5][C@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH2:7][C:8]#[CH:9])[C:3]1=[O:18].[CH2:19]([O:21][C:22]1[CH:23]=[CH:24][C:25]([F:36])=[C:26]([C:28]2[CH:33]=[C:32]([CH3:34])[N:31]=[C:30](I)[N:29]=2)[CH:27]=1)[CH3:20].N(CC)CC>C1COCC1.CCOC(C)=O.CCCC(C)C.[Cu](I)I>[CH2:19]([O:21][C:22]1[CH:23]=[CH:24][C:25]([F:36])=[C:26]([C:28]2[CH:33]=[C:32]([CH3:34])[N:31]=[C:30]([C:9]#[C:8][CH2:7][C@@:4]3([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:5][CH2:6][N:2]([CH3:1])[C:3]3=[O:18])[N:29]=2)[CH:27]=1)[CH3:20]
参加物反応条件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 8021DiethylamineHCID 900151884-(5-Ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidineHCID 90015672tert-Butyl N-[(3R)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate

生成物 1

HCID 90015138tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate収率 90.9%

試薬・触媒・溶媒 3

HCID 83717
Copper 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 (26.27 mg, 0.14 mmol), followed by PdCl2(Ph3P)2 (48.41 mg, 0.07 mmol) was added portionwise to a solution of the tert-butyl N-[(3R)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in Description 10) (348 mg, 1.38 mmol), 4-(5-ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidine (which may be prepared as described in D17) (642.17 mg, 1.79 mmol) and Et2NH (0.71 mL, 6.9 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The solvent was evaporated and the residue was dissolved in EtOAc and washed with water. The organic layer was dried (Na2SO4) and the solvent was evaporated to afford an oil. This was purified on a Biotage SP4 using a 25 g SNAP cartridge, eluting with 50 to 100% EtOAc/i-hexane affording the tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate (D18) (605 mg, 1.2538 mmol, 90.9% yield) as a pale yellow foam.

後処理

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with water
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customthe solvent was evaporated
  6. customto afford an oil
  7. customThis was purified on a Biotage

出典と根拠

ORDレコード
ord-77f06b83645d4068a9e8dcc4dd6fdcc2
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09309254B2

反応ノート

読み込み中…

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