Diisopropylamine → Thiazole-5-carboxylic acid (2-(4-(2-cyclobutoxy-pyrimidin-5-ylethynyl)-phenyl)-1-methyl-ethyl)-amide

HRID 76208Notes

Reaction equation

I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:11][C:12]([C:14]2[S:18][CH:17]=[N:16][CH:15]=2)=[O:13])[CH3:10])=[CH:4][CH:3]=1.C(NC(C)C)(C)C.[CH:26]1([O:30][C:31]2[N:36]=[CH:35][C:34]([C:37]#[CH:38])=[CH:33][N:32]=2)[CH2:29][CH2:28][CH2:27]1>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.[Cu]I.C1COCC1>[CH:26]1([O:30][C:31]2[N:32]=[CH:33][C:34]([C:37]#[C:38][C:2]3[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:11][C:12]([C:14]4[S:18][CH:17]=[N:16][CH:15]=4)=[O:13])[CH3:10])=[CH:4][CH:3]=3)=[CH:35][N:36]=2)[CH2:27][CH2:28][CH2:29]1

Participants

Conditions

Temperature: 0 °C

Procedure

100 mg (0.27 mmol) thiazole-5-carboxylic acid (2-(4-iodophenyl)-1-methylethyl)-amide (I76) are added to 2.0 mL THF and cooled down to 0° C. 2.87 mg (4.00 μmol) bis(triphenylphosphine)palladium dichloride, 1.02 mg (5.00 μmol) CuI, 90.6 μL (0.65 mmol) diisopropylamine and finally 51.5 mg 2-cyclobutoxy-5-ethynyl-pyrimidine (I25.7) are added and the reaction mixture is stirred at r.t. over night. The solvent is removed in vacuo and the residue is dissolved in EtOAc and washed with diluted ammonia solution (1×) and water (2×). The organic layer is dried with MgSO4 and the solvent is removed in vacuo. The crude product is purified by HPLC (MeOH/H2O/TFA).

Workup

customThe solvent is removed in vacuo
dissolutionthe residue is dissolved in EtOAc
washwashed with diluted ammonia solution (1×) and water (2×)
dry with materialThe organic layer is dried with MgSO4
customthe solvent is removed in vacuo
customThe crude product is purified by HPLC (MeOH/H2O/TFA)

Sources & evidence

ORD record: ord-0913b4b2d62a4d428a2cb55c04ee9ed9
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835472B2

Reaction notes

Loading…