Triethylamine → (R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8 (1H)-dicarboxylate

HRID 1468929ノート

反応式

HRID 1468929 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:4][C:3]=1[N:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:18]([CH:29]([CH3:31])[CH3:30])[C:17]1=O.CCN(CC)CC.[Si](Cl)(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>ClCCl>[CH:29]([C@H:18]1[N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[CH2:20][CH2:21][N:16]2[C:3]3[CH:4]=[C:5]([S:12]([CH3:15])(=[O:13])=[O:14])[C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:7][C:2]=3[N:1]=[C:17]12)([CH3:30])[CH3:31]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 24816Silicon tetrachlorideHCID 516892Sodium BicarbonateHCID 89827925(R)-tert-butyl 4-(2-amino-4-(methoxycarbonyl)-5-(methylsulfonyl)phenyl)-2-isopropyl-3-oxopiperazine-1-carboxylate

生成物 1

HCID 89815749(R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8 (1H)-dicarboxylate収率 55%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a 1 L round-bottom flask containing (R)-tert-butyl 4-(2-amino-4-(methoxycarbonyl)-5-(methylsulfonyl)phenyl)-2-isopropyl-3-oxopiperazine-1-carboxylate (25 g, 0.0532 mol) in dichloromethane (500 mL) were added Et3N (64.5 g, 0.638 mol, 12 eq.) and SiCl4 (27.1 g, 0.160 mol, 3 eq.). The mixture was stirred at rt overnight. The mixture was added dropwise to aq. NaHCO3 solution (54.1 g in 1 L of water, 0.644 mol, 12.1 eq.) at 0° C. slowly and adjusted to pH=8. The mixture was filtered and the aqueous layer was extracted with dichloromethane (3×600 mL). The combined organic layers were washed with brine, and then dried over anhydrous Na2SO4. The mixture was filtered and concentrated under vacuum to give the residue. The residue was purified by column chromatography on silica gel eluting with petroleum ether: EtOAc 2:1 to give (R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8(1H)-dicarboxylate (13.2 g, 55% yield) as a pale yellow solid. Analytical chiral HPLC: tR=9.03 min in 15 min chromatography (Method: OD-3—3—5—40—2.5ML). LC-MS MS (ESI) m/z 452.2 [M+H]+. 1H NMR (CD3OD 400 MHz): δ 8.31 (s, 1H), 8.01 (s, 1H), 5.30-5.18 (m, 1H), 4.70-4.52 (m, 1H), 4.47 (dd, J=3.2 and 12.4 Hz, 1H), 4.18 (dt, J=5.2 and 11.6 Hz, 1H), 3.98 (s, 3H), 3.70-3.52 (m, 1H), 3.44 (s, 3H), 2.50-2.38 (m, 1H), 1.53 (s, 9H), 1.25 (d, J=6.8 Hz, 3H), 1.06 (d, J=6.8 Hz, 3H).

後処理

  1. filtrationThe mixture was filtered
  2. extractionthe aqueous layer was extracted with dichloromethane (3×600 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated under vacuum
  7. customto give the residue
  8. customThe residue was purified by column chromatography on silica gel eluting with petroleum ether: EtOAc 2:1

出典と根拠

ORDレコード
ord-07cffe2f74bf46acbe69fd981c5b3172
出典データセット
uspto-grants-2015_04
特許番号
US09006245B2

反応ノート

読み込み中…