Formaldehyde → 6-(Imidazo[1,2-a]pyridin-3-ylmethyl)-2-(methylthio)benzo[d]thiazole

HRID 1848002Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]=O.[C:10]([C:12]1[CH:22]=[CH:21][C:15]2[N:16]=[C:17]([S:19][CH3:20])[S:18][C:14]=2[CH:13]=1)#[CH:11]>C1(C)C=CC=CC=1.Cl[Cu].C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Cu+2]>[N:1]1[CH:8]=[C:11]([CH2:10][C:12]2[CH:22]=[CH:21][C:15]3[N:16]=[C:17]([S:19][CH3:20])[S:18][C:14]=3[CH:13]=2)[N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=12

Participants

Conditions

Temperature: 120 °C

Procedure

A stirred mixture of 2-aminopyridine (100 mg, 1.1 mmol), paraformaldehyde (34 mg, 1.1 mmol), CuCl (5 mg, 0.06 mmol), and Cu(OTf)2 (19 mg, 0.06 mmol) in 3 mL of toluene in a pressure tube was flushed with argon. 6-Ethynyl-2-(methylthio)benzo[d]thiazole (327 mg, 1.6 mmol) from Step 3 of this Example was added. The reaction vessel was sealed and the mixture was heated in an oil bath at 120° C. for 6 h. LCMS analysis showed that the reaction was mostly complete. The reaction mixture was partitioned between EtOAc and saturated aq NaHCO3. The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc in hexanes to afford 6-(imidazo[1,2-a]pyridin-3-ylmethyl)-2-(methylthio)benzo[d]thiazole (127 mg, 38%) as a brown oil. LCMS (ESI) m/z 312 (M+H)+.

Workup

customwas flushed with argon
customThe reaction vessel was sealed
customThe reaction mixture was partitioned between EtOAc and saturated aq NaHCO3
washThe organic layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography
washeluting with 0-100% EtOAc in hexanes

Sources & evidence

ORD record: ord-36ffaa4090384c57935bbcd0a0b18781
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952058B2

Reaction notes

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