(+-)-Tetrahydro-2-furoic acid → {4-[6-(2-Fluoro-4-methanesulfonyl-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidin-1-yl}-(tetrahydro-furan-2-yl)-methanone

Participants

Role	Name	HCID	Charge
Reactant	(+-)-Tetrahydro-2-furoic acid	HCID 86079	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	4-(2-Fluoro-4-methanesulfonyl-phenoxy)-5-methyl-6-(piperidin-4-yloxy)-pyrimidine	HCID 67202021	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	{4-[6-(2-Fluoro-4-methanesulfonyl-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidin-1-yl}-(tetrahydro-furan-2-yl)-methanone	HCID 59856677	81.3%

Reaction Conditions

Temperature	120 °C

Reaction Steps

Mixture of 4-(2-fluoro-4-methanesulfonyl-phenoxy)-5-methyl-6-(piperidin-4-yloxy)-pyrimidine (76 mg, 0.2 mmole), tetrahydro-furan-2-carboxylic acid (0.26 mmole, 1.3 eq), HATU (0.26 mmole, 1.3 eq), and TEA (0.4 mmole, 2 eq) in 2 mL THF was heated under microwave irradiation at 120° C. for 30 minutes. Mixture was purified by HPLC to give compound C164 as a yellow solid (78 mg, 81%). 1H NMR (CDCl3, 400 MHz) δ 1.85-2.17 (m, 8H), 2.21 (s, 3H), 3.10 (s, 3H), 3.75-3.80 (m, 2H), 3.86-3.91 (m, 2H), 3.96-4.01 (m, 2H), 4.68 (t, 1H), 5.40-5.45 (m, 1H), 7.44 (t, 1H), 7.78-7.82 (m, 2H), 8.21 (s, 1H). Exact mass calculated for C22H26FN3O6S 479.2, found 480.3 (MH+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07470699B2
Source dataset	uspto-grants-2008_12
ORD ID	ord-0b2647ab1758481d88a44aca8096ded2
Source note	uspto-grants-2008_12