Water → (S)-3-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]amino}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 409505ノート

反応式

HRID 409505 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([N:13]([CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=2)[C:14]2[N:19]=[CH:18][C:17](Br)=[CH:16][N:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:36][N:37]1[CH:41]=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[N:38]1.C(=O)([O-])O.[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([N:13]([CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=2)[C:14]2[N:19]=[CH:18][C:17]([C:40]3[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=3)=[CH:16][N:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59614426(S)-3-[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 59614371(S)-3-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]amino}-pyrrolidine-1-carboxylic acid tert-butyl ester収率 61%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
95 °C

実験手順

To a mixture of (S)-3-[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester (2.2 mmol, 1.28 g), 1-methylpyrazol-3-yl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.7 mmol, 0.72 g), tetrakis(triphenylphosphine)palladium(0) (0.22 mmol, 260 mg) and 2M aqueous sodium hydrogen carbonate (3.2 mL) in 1,2-dimethoxy-ethane (15 mL) is allowed to warm to 95° C. and stirred for 3 hours. The mixture is cooled to room temperature and then added water. The mixture is extracted with CH2Cl2. The combined organic layer is dried over Na2SO4, filtrated, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give (S)-3-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]amino}-pyrrolidine-1-carboxylic acid tert-butyl ester 766 mg, 61%). ESI-MS m/z: 571 [M+1]+, Retention time 2.25 min (condition A).

後処理

  1. temperatureThe mixture is cooled to room temperature
  2. extractionThe mixture is extracted with CH2Cl2
  3. dry with materialThe combined organic layer is dried over Na2SO4
  4. filtrationfiltrated
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

出典と根拠

ORDレコード
ord-b471653331704a0bb085759a44702bfa
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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