Tributylstannane → 3-(2-Tert-butyl-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluoroaniline

HRID 590036Notes

Reaction equation

HRID 590036 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[C:18]([F:30])=[C:19]([NH:23]C(=O)OCC=C)[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1.C([SnH](CCCC)CCCC)CCC>C(Cl)Cl.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=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[C:18]([F:30])=[C:19]([CH:20]=[CH:21][CH:22]=2)[NH2:23])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 5948TributylstannaneHCID 579897172-Propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}carbamate

Product 1

HCID 579898453-(2-Tert-butyl-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluoroanilineYield 82%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

In a round bottom flask 2-propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}carbamate (800 mg, 1.79 mmol) was dissolved in DCM (30 mL) and water (0.5 ml). Tri-n-butyltin hydride (0.480 mL, 1.79 mmol) was added followed by tetrakis(triphenylphosphine)palladium (0) (103 mg, 0.090 mmol). This mixture was stirred 3 h at rt. By TLC all starting material is consumed. The reaction was concentrated to dryness. The crude was then dissolved into a small amount of DCM and injected onto a 25 g silica gel column. The column was eluted with EtOAc and hexanes. The title compound was obtained (0.594 g, 1.47 mmol, 82% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (d, J=5.3 Hz, 1H), 6.96-7.08 (m, 2H), 6.91 (t, J=8.2 Hz, 1H), 6.64 (t, J=6.7 Hz, 1H), 5.33 (s, 2H), 1.44 (s, 9H).

Workup

  1. customBy TLC all starting material is consumed
  2. concentrationThe reaction was concentrated to dryness
  3. dissolutionThe crude was then dissolved into a small amount of DCM
  4. washThe column was eluted with EtOAc and hexanes

Sources & evidence

ORD record
ord-25e693cf8ae142c1b07dcd81f40fcddb
Source dataset
uspto-grants-2016_01
Patent number
US09233956B2

Reaction notes

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