Hydrazine → HCID 11662095, compound

HRID 2102370Notes

Reaction equation

HRID 2102370 reaction equation
S(Cl)(Cl)=O.[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:20]3[C:19]([O:21][CH2:22][CH2:23][CH2:24][O:25][C:26]4[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=4)[C:29]([OH:31])=O)=[N:18][CH:17]=[N:16][C:15]=3[S:14][CH:13]=2)=[CH:8][CH:7]=1.[NH2:35][NH2:36]>O1CCCC1>[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[C:20]3[C:19]([O:21][CH2:22][CH2:23][CH2:24][O:25][C:26]4[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=4)[C:29]([NH:35][NH2:36])=[O:31])=[N:18][CH:17]=[N:16][C:15]=3[S:14][CH:13]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 24386Thionyl ChlorideHCID 11611575HCID 11611575, compound

Product 1

HCID 11662095HCID 11662095, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Thionyl chloride (13 mg, 0.11 mmol) was added to a solution of 3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propoxy)benzoic acid (43 mg, 0.10 mmol) in tetrahydrofuran (2.0 mL) with stirring at 70° C. Stirring continued for one hour at 70° C. and then the mixture was cooled to 25° C. and added to a solution of hydrazine (32 mg, 1.0 mmol) in tetrahydrofuran (2.0 mL). The reaction was stirred at room temperature for one hour and the solvent was then removed in vacuo. The residue was dissolved in ethyl acetate (30 mL), washed with of aqueous sodium bicarbonate solution (20 mL), concentrated, and purified by column chromatography over silica gel using 2% methanol in ethyl acetate as eluant to give 22 mg (50%) of 3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propoxy)benzohydrazide as a white solid. MS [M+H] 439.2, 1H NMR (CDCl3) δ (ppm) 8.65 (s, 1H), 7.50-7.35 (m, 2H), 7.32-7.21 (m, 3H), 7.18 (s, 1H), 7.10-6.97 (m, 2H), 6.94 (d, J=2.7 Hz, 1H), 4.59 (t, J=6.9 Hz, 2H), 4.11 (s, 2H), 3.74 (t, J=6.0 Hz, 2H), 2.09 (m, 2H).

Workup

  1. stirringStirring
  2. temperaturethe mixture was cooled to 25° C.
  3. stirringThe reaction was stirred at room temperature for one hour
  4. customthe solvent was then removed in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (30 mL)
  6. washwashed with of aqueous sodium bicarbonate solution (20 mL)
  7. concentrationconcentrated
  8. custompurified by column chromatography over silica gel using 2% methanol in ethyl acetate as eluant

Sources & evidence

ORD record
ord-b0cdce96e9ca4a32ade6f7ff6d6ef917
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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