Acetone → HCID 178458516、化合物

HRID 1508018ノート

反応式

HRID 1508018 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=2)[CH:3]=1.C([Mg]Cl)(C)C.C([Li])(C)(C)C.[CH3:34][C:35]([CH3:37])=[O:36].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[C:18]1([C:4]2[CH:3]=[C:2]([C:35]([OH:36])([CH3:37])[CH3:34])[CH:7]=[CH:6][C:5]=2[NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=1

参加物

8

反応物 5

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 178418306HCID 178418306、化合物HCID 178418918HCID 178418918、化合物HCID 178510376HCID 178510376、化合物

生成物 1

HCID 178458516HCID 178458516、化合物収率 68%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide (as prepared in the previous step, 50.0 mg, 0.135 mmol) in 2 mL of THF at −78° C. under Ar was added isopropyl magnesium chloride (71 μL, 0.14 mmol, 2.0 M in THF). The resulting mixture was warmed to RT and stirred for 15 min, cooled to −78° C. again. To the mixture was added tert-butyllithium (240 μL, 0.405 mmol, 1.7 M in pentane) and the resulting mixture was stirred at −78° C. for 5 min and then acetone (0.40 mL, 0.68 mmol) was added. The reaction was warmed to RT and stirred for 1 h under Ar. The mixture was treated with 1 mL of saturated NH4Cl followed by 40 mL of EtOAc and washed with H2O (10 mL), brine (5 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-2% MeOH/DCM) gave 32.1 mg (68%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 11.88 (s, 1H), 9.58 (s, 1H), 8.29 (d, 1H, J=8.6 Hz), 7.74 (s, 1H), 7.42 (dd, 1H, J=8.6, 2.2 Hz), 7.35 (d, 1H, J=2.2 Hz), 5.87 (m, 1H), 2.23-2.34 (m, 4H), 1.73-1.90 (m, 4H), 1.79 (s, 1H, OH), 1.61 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C20H22N4O2, 351.2 (M+H). found 351.0.

後処理

  1. temperaturecooled to −78° C. again
  2. stirringthe resulting mixture was stirred at −78° C. for 5 min
  3. temperatureThe reaction was warmed to RT
  4. stirringstirred for 1 h under Ar
  5. washwashed with H2O (10 mL), brine (5 mL)
  6. dry with materialdried (Na2SO4)
  7. customRemoval of the solvent under reduced pressure

出典と根拠

ORDレコード
ord-96932843ff8b42c2a4a2d06875f53638
出典データセット
uspto-grants-2015_12
特許番号
US09221797B2

反応ノート

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