Acetic Acid → HCID 178491036, compound

HRID 460349

Reaction equation

HRID 460349 reaction equation
[OH:1][CH:2]([CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[C:10](=O)[CH2:9][CH2:8]2.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([N:31]=[C:32]=S)[CH:28]=[CH:29][CH:30]=1.C[Si](C)(C)[Si](C)(C)C.[Li].[NH2:43][NH2:44].C(O)(=O)C>O.C1COCC1>[CH3:15][O:14][C:13]1[CH:12]=[C:11]2[C:7]([CH2:8][C:9]3[C:10]2=[N:43][NH:44][C:32]=3[NH:31][C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([O:24][CH3:23])[CH:26]=2)=[CH:6][C:5]=1[O:4][CH2:3][CH:2]([OH:1])[CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 9321HydrazineHCID 1378323-Methoxyphenyl isothiocyanate2×HCID 184456745-(2-Hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-indan-1-one2×HCID 57425481Lithium hexamethyldisilane

Product 1

HCID 178491036HCID 178491036, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 5-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-6-methoxy-indan-1-one (Intermediate N) (0.16 g, 0.0005 mole), 3-methoxy-phenyl isothiocyanate (Compound 19a) (0.08 mL, 0.0006 mole) and THF (1.5 mL) was added to lithium hexamethyldisilane (0.7 mL, 0.0007 mole) dropwise at room temperature with stirring. The reaction mixture was stirred for 4 hrs. Hydrazine (0.035 mL, 0.0011 mole) and acetic acid (0.66 mL, 0.0011 mole) were added to the reaction mixture. The reaction mixture was then heated at the reflux temperature for 18 hrs. To the resulting mixture was first added water (10 mL) and then the reaction mixture was 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 by reverse phase HPLC. Lyophilization yielded the title compound, 1-[7-Methoxy-3-(3-methoxy-phenylamino)-2,4-dihydro-indeno[1,2-c]pyrazol-6-yloxy]-3-pyrrolidin-1-yl-propan-2-ol as a white powder. MS m/z 451 (M+H)+; 1HNMR (DMSO-d6): 1.89(m, 2H), 2.02(m, 2H), 3.12(m, 2H), 3.34(m, 2H), 3.45(s, 2H), 3.62(s, 2H), 3.70(s, 3H), 3.85(s, 3H), 4.00(m, 2H), 4.20(m, 2H), 6.37(d, 1H), 6.71(d, 1H), 6.78(s, 1H), 7.10(t, 1H), 7.25(s, 1H), 7.3(s, 1H), 8.68(br s, 1H), 9.60(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. extractionthe reaction mixture was extracted 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 by reverse phase HPLC

Sources & evidence

ORD record
ord-2f11a91810be40269cd533c64ef6fa49
Source dataset
uspto-grants-2007_03
Patent number
US07196110B2

Linked notes

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