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

HRID 1961737Notes

Reaction equation

HRID 1961737 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[CH:17]=[C:18]([NH:22]C(=O)OCC=C)[CH:19]=[CH:20][CH:21]=2)[CH:5]=[CH:4][N:3]=1.C([SnH](CCCC)CCCC)CCC.CC(O)=O>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.C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[CH:17]=[C:18]([CH:19]=[CH:20][CH:21]=2)[NH2:22])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 5948TributylstannaneHCID 57989663HCID 57989663, compound

Product 1

HCID 579900463-[5-(2-Chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]anilineYield 80.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution containing 2-propen-1-yl {3-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]phenyl}carbamate (5.3 g, 12.77 mmol) and DCM (225 mL) was added tri-n-butyltin hydride (5.95 g, 20.43 mmol), followed by trans-dichlorobis(triphenylphosphine)palladium (II) (0.53 g, 0.64 mmol) and HOAc (1.84 g, 30.65 mmol). At the conclusion of the reaction, silica was added and the volatiles removed under reduced pressure. The residue was purified by flash column chromatography with (84% DCM, 15% MeOH, and 1% NH4OH): DCM 0% to 100% to afford 3.4 g of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ 8.57 (d, J=5.1 Hz, 1H), 7.16 (d, J=5.1 Hz, 1H), 7.10 (t, J=7.7 Hz, 1H), 6.72-6.75 (m, 1H), 6.64-6.69 (m, 1H), 6.60-6.63 (m, 1H), 5.28 (s, 2H), 3.27-3.40 (m, 1H), and 1.38 (d, J=7.0 Hz, 6H). MS (ESI): 331 [M+H]+.

Workup

  1. customAt the conclusion of the reaction, silica
  2. additionwas added
  3. customthe volatiles removed under reduced pressure
  4. customThe residue was purified by flash column chromatography with (84% DCM, 15% MeOH, and 1% NH4OH)

Sources & evidence

ORD record
ord-b92fe690e37b4e668c3b56a791fac509
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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