4-(Methanesulfonyl)phenylboronic acid → 6-(4-(Methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 1889767Notes

Reaction equation

HRID 1889767 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([NH2:11])[N:10]=2)[CH:7]=1.[CH3:12][S:13]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)(=[O:15])=[O:14]>>[CH3:12][S:13]([C:16]1[CH:21]=[CH:20][C:19]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([N:8]=[C:9]([NH2:11])[N:10]=3)[CH:7]=2)=[CH:18][CH:17]=1)(=[O:15])=[O:14]

Participants

3

Reactant 2

HCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 252159406-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 674814896-(4-(Methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Procedure

N-(5-bromo-2-pyridinyl)-N′-carboethoxy-thiourea was prepared from 2-amino-5-bromopyridine (10.0 g, 0.0578 mol) in a manner analogous to Step 2a. The reaction product was isolated as a yellow solid and used without further purification. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 12.14 (br s, 1H), 11.72 (br s, 1H), 8.67-8.55 (m, 1H), 8.53 (d, J=2.4 Hz, 1H), 8.13 (dd, J=9.0, 2.5 Hz, 1H), 4.23 (q, J=7.0 Hz, 2H), 1.26 (t, J=7.0 Hz, 3H). MS=304, 306 (MH)+. 36b) 6-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was prepared from N-(5-bromo-2-pyridinyl)-N′-carboethoxy-thiourea in a manner analogous to Step 2b. The reaction product was isolated as a white solid (7.84 g, 63%). MP=187-189° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.92 (d, J=1.9 Hz, 1H), 7.55 (dd, J=9.2, 1.9 Hz, 1H), 7.33 (d, J=9.4 Hz, 1H), 6.13 (br s, 2H). MS=213, 215 (MH)+. 36c) 6-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was prepared from 6-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (200.0 mg, 0.9388 mmol) and (4-methylsulfonylphenyl)boronic acid (210.0 mg, 1.050 mmol) in a manner analogous to Step 2c. The reaction product was isolated as an off-white solid (0.158 g, 58%). MP=301-303° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.08-9.05 (m, 1H), 8.06-7.97 (m, 4H), 7.86 (dd, J=9.2, 1.7 Hz, 1H), 7.48 (d, J=9.1 Hz, 1H), 6.15 (s, 2H), 3.26 (s, 3H). MS=289 (MH)+. 36d) 6-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(4-morpholin-4-yl-phenyl)-amine was prepared from 6-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (50.0 mg, 0.173 mmol) and 4-(4-bromo-phenyl)-morpholine (51.0 mg, 0.211 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (20.0 mg, 0.0366 mmol) as the ligand in a manner analogous to Step 2d. The title compound was isolated as a yellow solid (0.011 g, 14%). MP=>300° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.41 (s, 1H), 9.28 (s, 1H), 8.09 (d, J=7.7 Hz, 2H), 8.03-7.96 (m, 3H), 7.64 (d, J=8.8 Hz, 1H), 7.59 (d, J=7.9 Hz, 2H), 6.93 (d, J=8.0 Hz, 2H), 3.77-3.71 (m, 4H), 3.28 (s, 3H), 3.05-3.00 (m, 4H). MS=450 (MH)+.

Sources & evidence

ORD record
ord-787a4ce2aff8492a98645068bb317d6b
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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