6-Bromo-5-methyltetrazolo[1,5-a]pyridine → 5-methyl-6-(6-(trifluoromethyl)-1H-indazol-4-yl)tetrazolo[1,5-a]pyridine

HRID 58110Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.Br[C:24]1[CH:25]=[CH:26][C:27]2[N:28]([N:31]=[N:32][N:33]=2)[C:29]=1[CH3:30]>O1CCOCC1.C([O-])(O)=O.[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:30][C:29]1[N:28]2[N:31]=[N:32][N:33]=[C:27]2[CH:26]=[CH:25][C:24]=1[C:9]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][NH:13]2

Participants

Conditions

Temperature: 130 °C

Procedure

To a 20 mL microwave vial was added a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (50 mg, 0.160 mmol), 6-bromo-5-methyltetrazolo[1,5-a]pyridine (34.1 mg, 0.160 mmol), and PdCl2(dppf) (6.59 mg, 8.01 μmol) in dioxane (4 mL) and aqueous saturated NaHCO3 (2 mL). The resulting yellow suspension was heated at 130° C. for 30 minutes in a microwave reactor. The reaction mixture was subsequently purified by preparative HPLC, eluting with a gradient of 45-65% acetonitrile in H2O (containing 10 mM NH4HCO3). The product fractions were combined and dried to give the title compound. 1H NMR (400 MHz, CD3OD) δ ppm 2.83 (s, 3H), 7.51 (d, J=1.01 Hz, 1H), 7.91 (d, J=9.09 Hz, 1H), 8.04 (s, 1H), 8.06 (s, 1H), 8.10 (dd, J=9.09, 0.76 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C14H9F3N6, 319.1. found 319.3.

Workup

additionTo a 20 mL microwave vial was added
customThe reaction mixture was subsequently purified by preparative HPLC
washeluting with a gradient of 45-65% acetonitrile in H2O (containing 10 mM NH4HCO3)
customdried

Sources & evidence

ORD record: ord-26be06578eed4b43956ecb43b2a60a52
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434743B2

Reaction notes

Loading…