Diisopropylethylamine → (2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester

HRID 409467ノート

反応式

HRID 409467 の反応式
[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([NH:14][CH2:15]C2C=CC=CC=2)[C@@H:8]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:6])([CH3:3])[CH3:2].[Br:29][C:30]1[CH:31]=[N:32]C(Cl)=[N:34][CH:35]=1.CCN(C(C)C)C(C)C>C(O)C.[Pd].CN(C=O)C.[Cl-].[Na+].O.CCOC(C)=O>[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([NH:14][C:15]2[N:32]=[CH:31][C:30]([Br:29])=[CH:35][N:34]=2)[C@@H:8]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:6])([CH3:3])[CH3:2]

参加物

9

反応物 3

HCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 59614354(2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester

生成物 1

HCID 59614351(2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester収率 40%

試薬・触媒・溶媒 5

HCID 23938Palladium触媒HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

A solution of (2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (0.16 mmol; 61 mg) in ethanol (5 mL) is hydrogenated over 10% palladium on carbon (6 mg) at 50° C. and atmospheric pressure. After 9.5 hours, the suspension is cooled to ambient temperature and purged with nitrogen. The reaction mixture is filtered and concentrated under reduced pressure. A mixture of the obtained material (46 mg), 5-bromo-2-chloropyrimidine (0.18 mmol; 34.8 mg) and DIPEA (0.32 mmol; 41.4 mg) in DMF (0.8 mL) is stirred at 100° C. for 4 hours and then at 120° C. for 8.5 hours, and cooled to ambient temperature. The solution is diluted with brine and EtOAc. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (n-hexane/EtOAc) to give (2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (28.6 mg, 40% in 2 steps); ESI-MS m/z: 447 [M++1], Retention time 2.36 min (condition A).

後処理

  1. custompurged with nitrogen
  2. filtrationThe reaction mixture is filtered
  3. concentrationconcentrated under reduced pressure
  4. waitat 120° C. for 8.5 hours
  5. temperaturecooled to ambient temperature
  6. extractionThe product is extracted three times with EtOAc
  7. washThe combined organic layer is washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by column chromatography on silica gel (n-hexane/EtOAc)

出典と根拠

ORDレコード
ord-14c4bc4514f64b79adea1c2025602fa1
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

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