Dimethylformamide → HCID 59767790, compound

HRID 2217281Notes

Reaction equation

HRID 2217281 reaction equation
CN(C=O)C.[C:6]([C:8]1([NH:11][C:12](=[O:40])[C@H:13]([CH2:35][C:36]([F:39])([CH3:38])[CH3:37])[NH:14][C@@H:15]([C:20]2[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=2)[C:16]([F:19])([F:18])[F:17])[CH2:10][CH2:9]1)#[N:7].Br[C:42]1[CH:47]=[CH:46][C:45]([CH:48]([OH:53])[C:49]([F:52])([F:51])[F:50])=[CH:44][CH:43]=1.C(=O)(O)[O-].[Na+]>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].ClCCl>[C:6]([C:8]1([NH:11][C:12](=[O:40])[C@H:13]([CH2:35][C:36]([F:39])([CH3:37])[CH3:38])[NH:14][C@@H:15]([C:20]2[CH:21]=[CH:22][C:23]([C:42]3[CH:47]=[CH:46][C:45]([CH:48]([OH:53])[C:49]([F:51])([F:52])[F:50])=[CH:44][CH:43]=3)=[CH:24][CH:25]=2)[C:16]([F:19])([F:18])[F:17])[CH2:9][CH2:10]1)#[N:7]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 112190241-(4-Bromophenyl)-2,2,2-trifluoroethanolHCID 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]pentanamide

Product 1

HCID 59767790HCID 59767790, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A stream of nitrogen was passed through a solution of DMF (4 mL), 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 described in step 3 of example 1 (150 mg), 1-(4-bromophenyl)-2,2,2-trifluoroethanol from step 1 in example 3 (92 mg) and 2 M Na2CO3 (750 μL) for 15 minutes followed by the addition of [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex (1:1) with dichloromethane (12 mg). The mixture was warmed to 80° C. for 3 hours under nitrogen. The mixture was cooled to room temperature, poured into ice (20 g) and saturated aqueous sodium bicarbonate (20 mL) and extracted with 50% ethyl acetate in diethyl ether (3×50 mL). The combined extracts were washed with brine and dried with magnesium sulfate. Removal of the solvent left a residue that was purified by chromatography on SiO2 using ethyl acetate and hexanes (20 to 50%) as eluent, followed by trituration using diethyl ether and hexanes to yield the title compound.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with 50% ethyl acetate in diethyl ether (3×50 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried with magnesium sulfate
  5. customRemoval of the solvent
  6. waitleft a residue that
  7. customwas purified by chromatography on SiO2

Sources & evidence

ORD record
ord-1fabcc0b9a674bf5ae5a4c4205b47dff
Source dataset
uspto-grants-2008_08
Patent number
US07407959B2

Reaction notes

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