Potassium Acetate → Tert-butyl 4-(3-(5-(6-methoxy-1-oxoisoindolin-2-yl)furan-2-carboxamido)pyridin-4-yl)piperazine-1-carboxylate

HRID 1184524Notes

Reaction equation

HRID 1184524 reaction equation
Br[C:2]1[O:6][C:5]([C:7]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][C:15]=2[N:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=[O:8])=[CH:4][CH:3]=1.[CH3:29][O:30][C:31]1[CH:39]=[C:38]2[C:34]([CH2:35][NH:36][C:37]2=[O:40])=[CH:33][CH:32]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])(=O)C.[K+]>O1CCOCC1.C(OCC)(=O)C.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:29][O:30][C:31]1[CH:39]=[C:38]2[C:34]([CH2:35][N:36]([C:2]3[O:6][C:5]([C:7]([NH:9][C:10]4[CH:11]=[N:12][CH:13]=[CH:14][C:15]=4[N:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)=[O:8])=[CH:4][CH:3]=3)[C:37]2=[O:40])=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 517044Potassium AcetateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 140056236-Methoxy-2,3-dihydro-1H-isoindol-1-oneHCID 67051404Tert-butyl 4-(3-(5-bromofuran-2-carboxamido)pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68161686Tert-butyl 4-(3-(5-(6-methoxy-1-oxoisoindolin-2-yl)furan-2-carboxamido)pyridin-4-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl 4-(3-(5-bromofuran-2-carboxamido)pyridin-4-yl)piperazine-1-carboxylate (1.3, 100 mg, 0.20 mmol), the 6-methoxy-2,3-dihydro-isoindol-1-one,(1.4, 1.2 equivalent), Tris(dibenzylideneacetone) dipalladium(0) (20 mg, 0.02 mmol), Xantphos (26 mg, 0.04 mmol), Potassium acetate (139 mg, 0.66 mmol) in 5 ml of Dioxane was heated to 85° C. for 16 hours. Resulting suspension was diluted with ethyl acetate and passed through a celite filter to remove insoluble solid. Organic layer was concentrated in vacuo. The crude compound was purified by Prep-LC to yield compound, tert-butyl 4-(3-(5-(6-methoxy-1-oxoisoindolin-2-yl)furan-2-carboxamido)pyridin-4-yl)piperazine-1-carboxylate (1.5). HPLC-MS tR=3.84 min (UV254 nm); Mass calculated for formula C28H31N5O6, 533.23; observed LCMS m/z 534.20(M+H).

Workup

  1. customResulting suspension
  2. filtrationfilter
  3. customto remove insoluble solid
  4. concentrationOrganic layer was concentrated in vacuo
  5. customThe crude compound was purified by Prep-LC

Sources & evidence

ORD record
ord-4839e7501a0140359ab91f8a32b7be6b
Source dataset
uspto-grants-2014_03
Patent number
US08669259B2

Reaction notes

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