Acetic Acid → 3-[5-(2-Chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-4-fluoroaniline

HRID 1961960Notes

Reaction equation

HRID 1961960 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([NH:24]C(=O)OCC=C)[CH:20]=[CH:21][C:22]=2[F:23])[CH:5]=[CH:4][N:3]=1.CC(O)=O.C([SnH](CCCC)CCCC)CCC>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([CH:20]=[CH:21][C:22]=2[F:23])[NH2:24])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 5948TributylstannaneHCID 579900372-Propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-4-fluorophenyl}carbamate

Product 1

HCID 579898213-[5-(2-Chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-4-fluoroanilineYield 85.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-4-fluorophenyl}carbamate (11 g, 24.6 mmol) in DCM (200 mL), HOAc (3.6 g, 59.2 mmol), Pd(PPh3)2Cl2 (345 mg, 0.5 mmol) were added. Then tri-n-butyl tin hydride (8.6 g, 29.6 mmol) was added dropwise to the mixture at 0° C. The mixture was stirred at rt for 30 min. The reaction was quenched by adding saturated NaHCO3 (100 mL) slowly. The two layers were separated. The aqueous layer was extracted with DCM (100 mL×2). The combined organic layers were washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure and washed with petroleum ether (200 mL) to afford the crude product, 3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-4-fluoroaniline (7.62 g, 85.3% yield), 7.4 g of which was used directly in the next step.

Workup

  1. customThe reaction was quenched
  2. additionby adding saturated NaHCO3 (100 mL) slowly
  3. customThe two layers were separated
  4. extractionThe aqueous layer was extracted with DCM (100 mL×2)
  5. washThe combined organic layers were washed with water and brine successively
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washwashed with petroleum ether (200 mL)

Sources & evidence

ORD record
ord-22599b801cb04978a591928151593401
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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