Dichloromethane → HCID 58869054, compound

HRID 2246787Notes

Reaction equation

HRID 2246787 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:12][C@H:13]([C:19]([NH:21][C:22]2([C:25]#[N:26])[CH2:24][CH2:23]2)=[O:20])[CH2:14][C:15]([F:18])([CH3:17])[CH3:16])[CH:9]([F:11])[F:10])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:40]=[CH:39][C:38]([C:41]3([C:44]([NH2:46])=[O:45])[CH2:43][CH2:42]3)=[CH:37][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>CN(C)C=O.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]>[NH2:46][C:44]([C:41]1([C:38]2[CH:39]=[CH:40][C:35]([C:2]3[CH:7]=[CH:6][C:5]([C@H:8]([NH:12][C@H:13]([C:19]([NH:21][C:22]4([C:25]#[N:26])[CH2:23][CH2:24]4)=[O:20])[CH2:14][C:15]([F:18])([CH3:16])[CH3:17])[CH:9]([F:11])[F:10])=[CH:4][CH:3]=3)=[CH:36][CH:37]=2)[CH2:42][CH2:43]1)=[O:45]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 68742134HCID 68742134, compoundHCID 86612238HCID 86612238, compound

Product 1

HCID 58869054HCID 58869054, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

N2-[(1S)-1-(4-bromophenyl)-2,2-difluoroethyl]-N1-(1-cyanocyclopropyl)-4-fluoro-L-leucinamide (11.2 g, 25.9 mmol), 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarboxamide (8.2 g, 28.5 mmol, 1:1 equiv) and 2M sodium carbonate solution (35.4 mL, 70.8 mmol, 2.7 equiv) were mixed in 225 mL N,N-dimethylformamide. The mixture was degassed 3 times with nitrogen, then [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride, 1:1 complex with dichloromethane (838 mg, 1.15 mmol, 0.044 equiv) was added and mixture degassed again 3 times with nitrogen, heated at 80° C. for 6 hours. The reaction mixture was poured into H2O (900 mL), extracted with ethyl acetate (2×250 mL) and dichloromethane (250 mL). Combined organic fractions were washed with brine, dried over sodium sulphate and evaporated. The residue was purified by flash chromatography, eluting first with 1:1 ethyl acetate/hexane, then with 9:1 ethyl acetate/dichloromethane. The light pink recovered solid was stirred in 150 mL of 1:1 ethyl acetate/dichloromethane for 2 hours and filtered to yield the title compound.

Workup

  1. customThe mixture was degassed 3 times with nitrogen
  2. custommixture degassed again 3 times with nitrogen
  3. additionThe reaction mixture was poured into H2O (900 mL)
  4. extractionextracted with ethyl acetate (2×250 mL) and dichloromethane (250 mL)
  5. washCombined organic fractions were washed with brine
  6. dry with materialdried over sodium sulphate
  7. customevaporated
  8. customThe residue was purified by flash chromatography
  9. washeluting first with 1:1 ethyl acetate/hexane
  10. customThe light pink recovered solid
  11. filtrationfiltered

Sources & evidence

ORD record
ord-0373ecf31d8e4ce0a736cc01a3d09652
Source dataset
uspto-grants-2010_03
Patent number
US07687524B2

Reaction notes

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