Tetrabutylammonium Fluoride → 1-(3-fluoro-5-vinylpyridin-2-yl)-N-(6-fluorobenzo[d]thiazol-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide

HRID 1942270Notes

Reaction equation

HRID 1942270 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:27])[C:5]([N:8]2[CH2:13][CH:12]=[C:11]([C:14]([NH:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:20]=4[N:21]=3)=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[F-].[CH2:29]([N+](CCCC)(CCCC)CCCC)[CH2:30]CC.C(B1OC(C)(C)C(C)(C)O1)=C>C1COCC1>[F:27][C:4]1[C:5]([N:8]2[CH2:13][CH:12]=[C:11]([C:14]([NH:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:20]=4[N:21]=3)=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=[C:2]([CH:29]=[CH2:30])[CH:3]=1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 593347941-(5-bromo-3-fluoropyridin-2-yl)-N-(6-fluorobenzo[d]thiazol-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide

Product 1

HCID 593347931-(3-fluoro-5-vinylpyridin-2-yl)-N-(6-fluorobenzo[d]thiazol-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

687 mg of 1-(5-bromo-3-fluoropyridin-2-yl)-N-(6-fluorobenzo[d]thiazol-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide 29 (1.52 mmol) and 0.05 eq. PdCl2dppf catalyst ([1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II), 0.08 mMol, Sigma-Aldrich) were placed in a 50 mL vial with a screw-top septum and suspended in 2 mL dry THF. 2 Eq. 1M tetrabutylammonium fluoride in THF (3.04 mL, Sigma-Aldrich) were then added and the vial heated to 65° C. 1.1 Eq. vinylboronic acid pinacol ester (1.6 mMol, Sigma-Aldrich) were added to the vial via a syringe and the reaction progressed over 18 hours. The reaction mixture was transferred to a 500 mL extraction funnel and diluted with 250 mL water. The compound was extracted with 2×100 mL EtOAc. The organic layer was dried over sodium sulfate and concentrated under vacuum. The residue was chromatographed with a gradient of EtOAc in hexane. The fractions containing desired product (visualized by LC/MS) were concentrated and used without further purification or characterization.

Workup

  1. extractionThe reaction mixture was transferred to a 500 mL extraction funnel
  2. additiondiluted with 250 mL water
  3. extractionThe compound was extracted with 2×100 mL EtOAc
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was chromatographed with a gradient of EtOAc in hexane
  7. additionThe fractions containing desired product (visualized by LC/MS)
  8. concentrationwere concentrated
  9. customused without further purification or characterization

Sources & evidence

ORD record
ord-0576c24e5793438e8cb4cf0ba0068748
Source dataset
uspto-grants-2013_03
Patent number
US08389549B2

Reaction notes

Loading…