2-(Methylthio)-4-(tributylstannyl)pyrimidine → 5-Bromo-3-(2-(methylthio)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529326Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2I.[CH3:18][S:19][C:20]1[N:25]=[C:24]([Sn](CCCC)(CCCC)CCCC)[CH:23]=[CH:22][N:21]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:22]1[CH:23]=[CH:24][N:25]=[C:20]([S:19][CH3:18])[N:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A glass microwave reaction vessel was charged with 5-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (2.04 g, 5.01 mmol), Pd(PPh3)4 (0.555 g, 0.480 mmol), CuI (0.130 g, 0.683 mmol) and 2-(methylthio)-4-(tributylstannyl)pyrimidine (2.23 g, 5.37 mmol, Frontier Scientific). DMF (6 mL) was added and the reaction mixture was sealed under argon and heated thermally at 100° C. for 6.5 h. The solvent was removed in vacuo and the residue was dissolved in MeOH, evaporated onto silica gel and purified by flash chromatography (Isco, (80 gram)) eluting with 2M NH3 in MeOH:DCM (0:1→1:19) to give 855 mg of a tan amorphous solid. m/z: 405.0 [M+1].

Workup

customA glass microwave reaction vessel
customthe reaction mixture was sealed under argon
customThe solvent was removed in vacuo
dissolutionthe residue was dissolved in MeOH
customevaporated onto silica gel
custompurified by flash chromatography (Isco, (80 gram))
washeluting with 2M NH3 in MeOH:DCM (0:1→1:19)

Sources & evidence

ORD record: ord-007ea0459bfa49a09fbb377175217bc1
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

Loading…