Acetic Acid → HCID 178486521、化合物

HRID 460344

反応式

HRID 460344 の反応式
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=O)=[CH:5][C:4]=1[O:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.[F:22][C:23]1[CH:24]=[C:25]([N:29]=[C:30]=S)[CH:26]=[CH:27][CH:28]=1.C[Si](C)(C)[Si](C)(C)C.[Li].[NH2:41][NH2:42].C(O)(=O)C>O.C1COCC1>[F:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[NH:42][N:41]=[C:9]3[C:10]4[C:6]([CH2:7][C:8]=23)=[CH:5][C:4]([O:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[C:3]([O:2][CH3:1])[CH:11]=4)[CH:26]=[CH:27][CH:28]=1

参加物

8

反応物 5

HCID 176Acetic AcidHCID 9321HydrazineHCID 98343-Fluorophenyl isothiocyanate2 回HCID 184458186-Methoxy-5-(3-pyrrolidin-1-yl-propoxy)-indan-1-one2 回HCID 57425481Lithium hexamethyldisilane

生成物 1

HCID 178486521HCID 178486521、化合物

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of 6-methoxy-5-(3-pyrrolidin-1-yl-propoxy)-indan-1-one (Intermediate K, 0.45 g, 0.00155 mole), 3-fluoro-phenyl isothiocyanate (Compound 4a) (0.19 mL, 0.0017 mole) and THF (1.5 mL) was added to lithium hexamethyldisilane (1.8 mL, 0.0018 mole) dropwise at room temperature with stirring. The reaction mixture was stirred for 4 hrs. Hydrazine (0.095 mL, 0.003 mole) and acetic acid (0.180 mL, 0.003 mole) were added to the reaction mixture. The reaction mixture was then heated at the reflux temperature for 18 hrs. The resulting mixture was first added to water (10 mL) and then extracted with CH2Cl2. The organic layers were combined and washed with aqueous NaHCO3 solution, then washed with water and brine solution, dried (Na2SO4), and solvent was removed in vacuo. The crude material was purified on the reverse phase HPLC. Lyophilization yielded the title compound, (3-Fluoro-phenyl)-[7-methoxy-6-(3-pyrrolidin-1-yl-propoxy)-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl]-amine as a white powder. MS m/z 423 (M+H)+; 1HNMR (DMSO-d6): 1.88(m, 2H), 2.00(m, 2H), 2.15(m, 2H), 3.02(m, 2H), 3.29(dd, 2H), 3.37(s, 2H), 3.61(m, 2H), 3.74(s, 3H), 4.04(t, 2H), 6.52(t, 1H), 6.93(d, 1H), 7.18(m, 4H), 8.8(br s, 1H), 9.7(br s, 1H).

後処理

  1. stirringThe reaction mixture was stirred for 4 hrs
  2. temperatureThe reaction mixture was then heated at the reflux temperature for 18 hrs
  3. extractionextracted with CH2Cl2
  4. washwashed with aqueous NaHCO3 solution
  5. washwashed with water and brine solution
  6. dry with materialdried (Na2SO4), and solvent
  7. customwas removed in vacuo
  8. customThe crude material was purified on the reverse phase HPLC

出典と根拠

ORDレコード
ord-245536502e4d40e99300a8b9531df57c
出典データセット
uspto-grants-2007_03
特許番号
US07196110B2

関連ノート

読み込み中…