Pyridine → 2-(3-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}phenyl)-5-methyl-1,3,4-thiadiazole

HRID 909511Notes

Reaction equation

HRID 909511 reaction equation
[C:1]([NH:4][NH:5][C:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[C:18]([C:20]3[NH:21][C:22]([C:25]4[S:26][CH:27]=[CH:28][N:29]=4)=[CH:23][CH:24]=3)[CH:17]=[C:16]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:15]=2)=[C:9]([F:36])[CH:8]=1)(=O)[CH3:2].COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:47]2)=CC=1.N1C=CC=CC=1>C1(C)C=CC=CC=1.C(#N)C>[F:36][C:9]1[CH:8]=[C:7]([C:6]2[S:47][C:1]([CH3:2])=[N:4][N:5]=2)[CH:12]=[CH:11][C:10]=1[O:13][C:14]1[CH:19]=[C:18]([C:20]2[NH:21][C:22]([C:25]3[S:26][CH:27]=[CH:28][N:29]=3)=[CH:23][CH:24]=2)[CH:17]=[C:16]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:15]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 87949Lawesson's reagentHCID 66682489N'-Acetyl-3-fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzohydrazide

Product 1

HCID 580655392-(3-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}phenyl)-5-methyl-1,3,4-thiadiazoleYield 70.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

N′-Acetyl-3-fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzohydrazide (40 mg, 0.076 mmol) synthesized in Example (49a) was dissolved in a mixed solvent of toluene (4.0 mL) and acetonitrile (2.0 mL), and 2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (45 mg, 0.111 mmol) and pyridine (0.03 mL, 0.372 mmol) were added, followed by stirring at 100° C. for 4 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=60%-80%) to afford the desired compound (28 mg, yield 70%) as a yellow solid.

Workup

  1. additionwere added
  2. temperatureThe reaction solution was cooled to room temperature
  3. distillationthe solvent was distilled off under reduced pressure
  4. customthe resulting residue was purified
  5. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=60%-80%)

Sources & evidence

ORD record
ord-b17c214d9eb44eb08825cd5ccb205aff
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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