Sodium Carbonate → HCID 86594563, compound

HRID 1744102Notes

Reaction equation

HRID 1744102 reaction equation
Br[C:2]1[CH:3]=[N:4][S:5][C:6]=1[NH:7][C@H:8]([C:13]([NH:15][CH2:16][C:17]#[N:18])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C([O-])([O-])=O.[Na+].[Na+]>CN(C)C=O.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]>[C:17]([CH2:16][NH:15][C:13](=[O:14])[C@H:8]([CH2:9][CH:10]([CH3:12])[CH3:11])[NH:7][C:6]1[S:5][N:4]=[CH:3][C:2]=1[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[N:29]1[CH2:28][CH2:27][N:26]([C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:25])[CH2:31][CH2:30]1)#[N:18]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 86594562HCID 86594562, compound

Product 1

HCID 86594563HCID 86594563, compoundYield 45.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of N2-(4-bromoisothiazol-5-yl)-N1-(cyanomethyl)leucinamide (91 mg, 0.27 mmol), 4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenylboronic acid (100 mg, 0.33 mmol, prepared as described in Example 1), PdCl2(dppf) (5 mg, 0.006 mmol) and 2.0 M Na2CO3 aqueous solution (0.17 mL, 0.34 mmol) were heated to 85° C. in N,N-dimethylformamide (0.80 mL) under a nitrogen atmosphere for a total of 8 h. During this period additional catalyst (5 mg) was introduced at the 2 h, 4 h and 6 h time points. The reaction mixture was then cooled to rt, diluted with water and extracted with ethyl acetate (3×). The combined extracts were washed with saturated sodium chloride solution, dried (Na2SO4) and concentrated. Flash chromatography of the residue on silica eluting with a mixture of acetone and benzene (1:4) afforded 63 mg of N1-(cyanomethyl)-N2-[4-(4-(tert-butoxycarbonyl)piperazin-1-ylphenyl)isothiazol-5-yl]leucinamide as a faint-tan foam.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined extracts were washed with saturated sodium chloride solution
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. additionFlash chromatography of the residue on silica eluting with a mixture of acetone and benzene (1:4)

Sources & evidence

ORD record
ord-ae0d471451124a779157ef7844ec5f93
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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