1,1-Dimethylethyl 4-(5-(2-chloro-4-pyrimidinyl)-4-{2-fluoro-3-[(3-furanylsulfonyl)amino]phenyl}-1,3-thiazol-2-yl)-4-methyl-1-piperidinecarboxylate → 1,1-Dimethylethyl 4-[4-{2-fluoro-3-[(3-furanylsulfonyl)amino]phenyl}-5-(2-methyl-4-pyrimidinyl)-1,3-thiazol-2-yl]-4-methyl-1-piperidinecarboxylate

HRID 239591Notes

Reaction equation

HRID 239591 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]3([CH3:26])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)=[N:10][C:9]=2[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([NH:33][S:34]([C:37]3[CH:41]=[CH:40][O:39][CH:38]=3)(=[O:36])=[O:35])[C:28]=2[F:42])[CH:5]=[CH:4][N:3]=1.[CH3:43][Zn]C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[F:42][C:28]1[C:29]([NH:33][S:34]([C:37]2[CH:41]=[CH:40][O:39][CH:38]=2)(=[O:36])=[O:35])=[CH:30][CH:31]=[CH:32][C:27]=1[C:9]1[N:10]=[C:11]([C:13]2([CH3:26])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[S:12][C:8]=1[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH3:43])[N:7]=1

Participants

5

Reactant 2

HCID 579899411,1-Dimethylethyl 4-(5-(2-chloro-4-pyrimidinyl)-4-{2-fluoro-3-[(3-furanylsulfonyl)amino]phenyl}-1,3-thiazol-2-yl)-4-methyl-1-piperidinecarboxylateHCID 178477796HCID 178477796, compound

Product 1

HCID 579899371,1-Dimethylethyl 4-[4-{2-fluoro-3-[(3-furanylsulfonyl)amino]phenyl}-5-(2-methyl-4-pyrimidinyl)-1,3-thiazol-2-yl]-4-methyl-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

1,1-dimethylethyl 4-(5-(2-chloro-4-pyrimidinyl)-4-{2-fluoro-3-[(3-furanylsulfonyl)amino]phenyl}-1,3-thiazol-2-yl)-4-methyl-1-piperidinecarboxylate (130 mg, 0.205 mmol) was dissolved into 1,4-dioxane (3 mL) and the solution was degassed for 10 min. PdCl2(dppf)-CH2Cl2 adduct (8.37 mg, 10.25 μmol) and dimethylzinc (0.205 mL, 0.410 mmol) were added the reaction mixture. The reaction mixture was stirred at 80° C. for 1 h. The reaction was quenched with methanol (3 mL) and water (10 mL) and extracted with EtOAc (3×). The extract was dried over Na2SO4, filtered, and concentrated. The residue was purified using column chromatography (40% to 100% EtOAc/hexane) to the title compound (100 mg). MS (ESI): 557.7 [M+1]+.

Workup

  1. customthe solution was degassed for 10 min
  2. customThe reaction was quenched with methanol (3 mL) and water (10 mL)
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe extract was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-7ee5a1a58e58404fa7515ebae5b1d9b4
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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