tert-Butyl piperazine-1-carboxylate → 4-[4-Methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 519182ノート

反応式

HRID 519182 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:25])[C:7](=[O:24])[N:8]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:9]=1.[N:26]1([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CC([O-])(C)C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1(C)C=CC=CC=1.C(O[Pd]OC(=O)C)(=O)C>[C:35]([O:34][C:32]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][CH:15]=2)[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:25])[C:7](=[O:24])[N:8]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:9]=2)[CH2:28][CH2:27]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

参加物

7

反応物 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 867274626-Bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

生成物 1

HCID 867275934-[4-Methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester収率 33.7%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

実験手順

To a mixture of 6-bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #1, Step E, 0.5 g, 1.173 mmol), tert-butyl piperazine-1-carboxylate (0.655 g, 3.52 mmol) and sodium 2-methylpropan-2-olate (0.225 g, 2.345 mmol) in toluene (50 mL) was added dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (0.224 g, 0.469 mmol) and diacetoxypalladium (0.026 g, 0.117 mmol) and the reaction mixture was heated at reflux overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 3-20% EtOAc in petroleum ether) to give 4-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.210 g, 33%). 1H NMR (400 MHz, CDCl3) δ 6.92 (d, J=8.8 Hz, 1H), 6.56 (dd, J=2.6, 8.7 Hz, 1H), 6.50 (d, J=2.5 Hz, 1H), 5.18-5.05 (m, 2H), 4.73 (q, J=6.6 Hz, 1H), 4.65-4.52 (m, 2H), 3.67 (t, J=8.4 Hz, 2H), 3.63-3.57 (m, 4H), 3.04 (d, J=4.0 Hz, 4H), 1.58 (s, 5H), 1.51-1.46 (m, 12H), 1.03-0.94 (m, 2H), 0.02 (s, 9H).

後処理

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux overnight
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (eluting with 3-20% EtOAc in petroleum ether)

出典と根拠

ORDレコード
ord-4c25b497c6ec4d309c397d2507c8f033
出典データセット
uspto-grants-2015_08
特許番号
US09115151B2

反応ノート

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