Tetrahydrofuran → Ethyl 3-{4-[4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinyl}propanoate

HRID 239489Notes

Reaction equation

HRID 239489 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=3[F:34])(=[O:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1.[Br-].[CH2:37]([O:39][C:40](=[O:44])[CH2:41][CH2:42][Zn+])[CH3:38].C1COCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:34][C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([F:33])[C:27]=1[S:24]([NH:23][C:19]1[C:18]([F:35])=[C:17]([C:9]2[N:10]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH2:42][CH2:41][C:40]([O:39][CH2:37][CH3:38])=[O:44])[N:7]=2)[CH:22]=[CH:21][CH:20]=1)(=[O:26])=[O:25]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 57989782N-(3-(5-(2-chloro-4-pyrimidinyl)-2-(1,1-diethylethyl)-1,3-thiazol-4-yl)-2-fluoraphenyl)-2,6-difluorobenzenesulfonamideHCID 178471816HCID 178471816, compound

Product 1

HCID 57990054Ethyl 3-{4-[4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinyl}propanoateYield 64%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

To solid N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (1 g, 1.85 mmol) was added 3-ethoxy-3-oxopropylzinc bromide 0.5M solution in THF (31.5 ml, 15.77 mmol) at RT. Bis(tri-t-butylphosphine)palladium (0) (0.095 g, 0.186 mmol) was added to reaction mixture. The reaction was stirred at RT for several hours. The reaction was check by LCMS. The reaction mixture was quenched into sat'd NH4Cl and stirred for several hours. A white/grey ppt was filtered. The EtOAc was added to filtrate. The EtOAc was separed contained form the water layer. The water layer was rewashed with EtOAc and the organic extracts combined, dried over MgSO4, filtered, and concentrated to dryness to give an orange oil. The crude product was added to a silica gel column and eluted with EtOAc with DCM (20% to 60%) and collected fractions to obtain ethyl 3-{4-[4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinyl}propanoate (1.12 g, 64%). MS (ESI): 605 [M+H]+.

Workup

  1. customThe reaction mixture was quenched into sat'd NH4Cl
  2. stirringstirred for several hours
  3. filtrationA white/grey ppt was filtered
  4. additionThe EtOAc was added to filtrate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customto give an orange oil
  9. washeluted with EtOAc with DCM (20% to 60%)
  10. customcollected fractions

Sources & evidence

ORD record
ord-328ce8af518949b1a295f40a1afb0011
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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