Acetic Acid → HCID 178486521, compound

HRID 1714437Notes

Reaction equation

HRID 1714437 reaction equation
[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

Participants

8

Reactant 5

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

Product 1

HCID 178486521HCID 178486521, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0119c50d093f4b46a9601f2163041bdc
Source dataset
uspto-grants-2010_09
Patent number
US07795440B2

Reaction notes

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