Diisopropylethylamine → N-[[2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-5-(2,6-dimethyl-4-pyridinyl)-4-thiazolyl]methyl]-3-methyl-5-isoxazolecarboxamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	3-Methyl-1,2-oxazole-5-carbonyl chloride	HCID 12905099	—
Reactant	[2-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazol-4-yl]-methylamine	HCID 67216071	—
Solvent	Dichloromethane	HCID 6344	—
Product	N-[[2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-5-(2,6-dimethyl-4-pyridinyl)-4-thiazolyl]methyl]-3-methyl-5-isoxazolecarboxamide	HCID 53237122	64%

Reaction Conditions

Temperature	0 °C

Reaction Steps

DIPEA (0.16 mL, 0.97 mmol) was added to a solution of Intermediate 5 (150 mg, 0.45 mmol) in DCM (6 mL). The reaction mixture was cooled to 0° C. under nitrogen atmosphere. 3-Methylisoxazole-5-carbonyl chloride (79 mg, 0.54 mmol) was then added dropwise and stirring was continued for 1 h at room temperature. The reaction was washed with sodium bicarbonate and then twice with water. The organic layer was dried over a magnesium sulphate plug and evaporated. The residue was purified by preparative HPLC (RP Shandon Hyperprep C18 BDS—8 μm, 250 g, 5 cm; mobile phase (0.25% NH4HCO3 solution in water, CH3CN)), yielding 127 mg (64%) of Compound 4.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08637510B2
Source dataset	uspto-grants-2014_01
ORD ID	ord-c37e071bf18a43a69220815a122cfa8e
Source note	uspto-grants-2014_01