Acetic Acid → HCID 178486521, 화합물

HRID 460344

반응식

HRID 460344 반응식
[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

참가 물질

8

반응물 5

HCID 176Acetic AcidHCID 9321HydrazineHCID 98343-Fluorophenyl isothiocyanate2회HCID 184458186-Methoxy-5-(3-pyrrolidin-1-yl-propoxy)-indan-1-one2회HCID 57425481Lithium hexamethyldisilane

생성물 1

HCID 178486521HCID 178486521, 화합물

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-245536502e4d40e99300a8b9531df57c
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07196110B2

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