(2S)-N-(1-Cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]amino]pentanamide → HCID 11613537, compound

HRID 971328Notes

Reaction equation

HRID 971328 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]2([C:10]([O:12]CC)=[O:11])[CH2:9][CH2:8]2)[N:6]=1.[C:15]([C:17]1([NH:20][C:21](=[O:49])[C@H:22]([CH2:44][C:45]([F:48])([CH3:47])[CH3:46])[NH:23][C@@H:24]([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[C:25]([F:28])([F:27])[F:26])[CH2:19][CH2:18]1)#[N:16]>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+].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:15]([C:17]1([NH:20][C:21]([C@@H:22]([NH:23][C@@H:24]([C:29]2[CH:30]=[CH:31][C:32]([C:2]3[S:3][CH:4]=[C:5]([C:7]4([C:10]([OH:12])=[O:11])[CH2:8][CH2:9]4)[N:6]=3)=[CH:33][CH:34]=2)[C:25]([F:26])([F:28])[F:27])[CH2:44][C:45]([F:48])([CH3:47])[CH3:46])=[O:49])[CH2:19][CH2:18]1)#[N:16]

Participants

6

Reactant 2

HCID 59767791(2S)-N-(1-Cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]amino]pentanamideHCID 69338992HCID 69338992, compound

Product 1

HCID 11613537HCID 11613537, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of ethyl 1-(2-bromo-1,3-thiazol-4-yl)cyclopropanecarboxylate (166 mg, 1.2 mmol) and N1-(1-cyanocyclopropyl)-4-fluoro-N2-{(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-L-leucinamide (Example 3, Step 3, 250 mg, 0.5 mmol) in DMF (5 mL) and 2M Na2CO3 (0.63 mL) was degassed with a stream of nitrogen for 10 min, then PdCl2(dppf) (41 mg 0.05 mmol) was added and the mixture heated to 80° C. for 8 h. The mixture was cooled and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic phase was washed with brine, dried over MgSO4 and evaporated. Purification by SiO2 chromatography (30% ethyl acetate/hexanes) provided the title compound.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customPurification by SiO2 chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b6aad4ee123f45de81cc4ec1ab343d4a
Source dataset
uspto-grants-2007_12
Patent number
US07312353B2

Reaction notes

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