Diisopropylethylamine → (4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-methanone

HRID 1967040ノート

反応式

HRID 1967040 の反応式
[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:3]=1[O:4][C:5]1[C:10]([C:11]([O-:13])=O)=[CH:9][N:8]=[C:7]([CH3:14])[CH:6]=1.[Li+].C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:54]1([N:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[NH:60][CH2:59][CH2:58]2)[CH2:56][CH2:55]1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH:54]1([N:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[N:60]([C:11]([C:10]3[CH:9]=[N:8][C:7]([CH3:14])=[CH:6][C:5]=3[O:4][C:3]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:2]=3[Cl:1])=[O:13])[CH2:59][CH2:58]2)[CH2:56][CH2:55]1

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2 回HCID 67320585Lithium 4-(2,5-dichloro-phenoxy)-6-methyl-nicotinateHCID 673207551-Cyclopropyl-1,2,3,4-tetrahydroquinoxaline

生成物 1

HCID 53259032(4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-methanone収率 60%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 420 mg (1.381 mmol) lithium 4-(2,5-dichloro-phenoxy)-6-methyl-nicotinate in 6 mL dry N,N-dimethylformamide was added 1.17 mL (6.907 mmol) N-ethyldiisopropylamine and 635 mg (1.658 mmol) 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 289 mg (1.658 mmol) 1-cyclopropyl-1,2,3,4-tetrahydro-quinoxaline (Example 8, intermediate a). The reaction mixture was stirred for 18 hours at room temperature and then poured on 30 mL 10% aqueous sodium bicarbonate solution and 30 mL ethyl acetate. The layers were separated and the aqueous layer was extracted a second time with 30 mL ethyl acetate. The organic layers were washed with 30 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) with gradient of n-heptane:ethyl acetate (100:0 to 0:100) to give 375 mg (60%) of the title compound as a light yellow solid. MS (ESI): m/z=454.108 [M+H]+.

後処理

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted a second time with 30 mL ethyl acetate
  3. washThe organic layers were washed with 30 mL brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-abc3187e567443f0af80f313b99ccdb2
出典データセット
uspto-grants-2013_04
特許番号
US08420647B2

反応ノート

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