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 519182노트

반응식

HRID 519182 반응식
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]

참가 물질

7

반응물 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

생성물 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 ester수율 33.7%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-4c25b497c6ec4d309c397d2507c8f033
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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