1,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylate → 1,1-Dimethylethyl 4-[4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-5-(2-methyl-4-pyrimidinyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylate

HRID 239596Notes

Reaction equation

HRID 239596 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]3[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:26]2[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][S:33]([C:36]3[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:37]=3[F:43])(=[O:35])=[O:34])[C:27]=2[F:44])[CH:5]=[CH:4][N:3]=1.[CH3:45][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:43][C:37]1[CH:38]=[CH:39][CH:40]=[C:41]([F:42])[C:36]=1[S:33]([NH:32][C:28]1[C:27]([F:44])=[C:26]([C:9]2[N:10]=[C:11]([CH:13]3[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)[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:45])[N:7]=2)[CH:31]=[CH:30][CH:29]=1)(=[O:35])=[O:34]

Participants

5

Reactant 2

HCID 579899421,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylateHCID 178477796HCID 178477796, compound

Product 1

HCID 579896871,1-Dimethylethyl 4-[4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-5-(2-methyl-4-pyrimidinyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylateYield 74%

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-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1,3-thiazol-2-yl]-1-piperidinecarboxylate (167 mg, 0.251 mmol) was dissolved into 1,4-dioxane (3 mL) and the solution was degassed for 10 min. PdCl2(dppf)-CH2Cl2 adduct (10.24 mg, 0.013 mmol) and dimethylzinc (0.251 mL, 0.501 mmol) were added to 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 give the title compound (120 mg). MS (ESI): 646.3 [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-53dd3f0fe65e44fa9d82fb8d2613766f
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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