Diethylamine → tert-Butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-3-yl]carbamate

HRID 626880ノート

反応式

HRID 626880 の反応式
I[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]1[CH2:23][CH2:22][C@@:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])([CH2:24][C:25]#[CH:26])[C:20]1=[O:35].N(CC)CC>C1COCC1.CCOC(C)=O.O.[Cu](I)I>[CH3:18][N:19]1[CH2:23][CH2:22][C@@:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])([CH2:24][C:25]#[C:26][C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)[CH:5]=[CH:4][N:3]=2)[C:20]1=[O:35]

参加物

8

反応物 3

HCID 8021DiethylamineHCID 89649283tert-Butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamateHCID 900151392-Iodo-4-[4-(trifluoromethyl)phenyl]pyrimidine

生成物 1

HCID 90015348tert-Butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-3-yl]carbamate収率 87.3%

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
20 °C

実験手順

Copper iodide (25.51 mg, 0.1300 mmol), followed by PdCl2(Ph3P)2 (47.01 mg, 0.0700 mmol) was added portionwise to a solution of 2-iodo-4-[4-(trifluoromethyl)phenyl]pyrimidine (which may be prepared as described in Description 6) (703.46 mg, 2.01 mmol), tert-butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in D4) (338 mg, 1.34 mmol) and Et2NH (0.69 mL, 6.7 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The reaction was diluted with EtOAc and water was added. The phases were separated and the organic layer was dried (Na2SO4) and the solvent evaporated to afford a brown oil. This was purified by using a Biotage SP4, with a 25 g SNAP cartridge, eluting with 0 to 100% EtOAc in i-hexane to afford tert-butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-3-yl]carbamate (D7) (555 mg, 1.17 mmol, 87.3% yield) as a yellow oil.

後処理

  1. additionwas added
  2. customThe phases were separated
  3. dry with materialthe organic layer was dried (Na2SO4)
  4. customthe solvent evaporated
  5. customto afford a brown oil
  6. customThis was purified
  7. washwith a 25 g SNAP cartridge, eluting with 0 to 100% EtOAc in i-hexane

出典と根拠

ORDレコード
ord-39a01eab1d944a53809930220691306b
出典データセット
uspto-grants-2016_04
特許番号
US09309254B2

反応ノート

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