Diisopropylamine → 3-Amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one

HRID 626893ノート

反応式

HRID 626893 の反応式
[NH2:1][C:2]1([CH2:9][C:10]#[CH:11])[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8].I[C:13]1[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[N:14]=1.C(NC(C)C)(C)C>COC(C)(C)C.[Cu](I)I.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1([CH2:9][C:10]#[C:11][C:13]2[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=3)[N:14]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]

参加物

7

反応物 3

HCID 7912DiisopropylamineHCID 896492053-Amino-1-methyl-3-prop-2-ynyl-pyrrolidin-2-oneHCID 90014635HCID 90014635、化合物

生成物 1

HCID 1180360983-Amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one収率 80.3%

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 178419050HCID 178419050、化合物触媒HCID 15413tert-Butyl methyl ether溶媒

実験手順

To a stirred solution of 3-amino-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one (which may be prepared as described in Description 3) (2.3 g, 15.11 mmol) in tert-butyl methyl ether (50 mL) was added 2-iodo-4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidine (which may be prepared as described in Description 12) (6.05 g, 16.62 mmol). diisopropylamine (6.35 mL, 45.34 mmol) was then added, followed by copper iodide (57.56 mg, 0.300 mmol) and bis(triphenylphosphine)palladium (II) dichloride (106.07 mg, 0.1500 mmol). The reaction was then stirred at room temperature for 5 days. The reaction mixture was transferred to a separating funnel and the flask washed with an additional quantity of tert-butyl methyl ether (15 ml). The organic solution was washed with water (2×50 mL) and brine (50 mL). The organic phase was dried over magnesium sulphate, filtered, and then the magnesium sulphate washed with dichloromethane (30 ml). The filtrate was concentrated at reduced pressure to give a yellow foam. The product was purified by silica gel chromatography eluting with ethyl acetate followed by an increasing percentage of a solution of 10% 0.880 ammonia in methanol, to give the title compound (D14b) as a yellow foam (4.71 g). This racemate was consistent by NMR and mass spectroscopy with the R isomer prepared in Description 14.

後処理

  1. customThe reaction mixture was transferred to a separating funnel
  2. washthe flask washed with an additional quantity of tert-butyl methyl ether (15 ml)
  3. washThe organic solution was washed with water (2×50 mL) and brine (50 mL)
  4. dry with materialThe organic phase was dried over magnesium sulphate
  5. filtrationfiltered
  6. washthe magnesium sulphate washed with dichloromethane (30 ml)
  7. concentrationThe filtrate was concentrated at reduced pressure
  8. customto give a yellow foam
  9. customThe product was purified by silica gel chromatography
  10. washeluting with ethyl acetate

出典と根拠

ORDレコード
ord-6fdcbbace1ee4c3f81a02084ad51b9b2
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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