4-Bromoanisole → 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-N-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 1889830Notes

Reaction equation

HRID 1889830 reaction equation
[O:1]=[S:2]1(=[O:25])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:20]4[N:21]=[C:22]([NH2:24])[N:23]=[C:19]4[CH:18]=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.Br[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>>[O:25]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:20]4[N:21]=[C:22]([NH:24][C:27]5[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=5)[N:23]=[C:19]4[CH:18]=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 77304-BromoanisoleHCID 674794405-[4-[(1,1-Dioxo-1,4-thiazinan-4-yl)methyl]phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 596123375-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-N-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridin-2-amineYield 43.1%

Procedure

5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine was prepared from 5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (368 mg, 1.73 mmol) and 4-[(4-boronophenyl)methyl]-thiomorpholine 1,1-dioxide (0.512 mg, 1.90 mmol), in a manner analogous to Step 73c. The residue was purified on a 12 g Isco silica gel column using a gradient of 0-15% methanol in dichloromethane as an eluent. 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine (490 mg, 79%) was isolated as a beige foam. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 7.93 (d, J=8.5 Hz, 2H), 7.50 (m, 3H), 7.37 (d, J=7.8 Hz, 1H), 7.07 (d, J=7.8 Hz, 1H), 6.02 (s, 2H), 3.78 (s, 2H), 3.15 (s, 4H), 2.91 (s, 4H). MS=358 (MH)+. 95b) 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine (50 mg, 0.140 mmol) and 1-bromo-4-methoxy benzene (29 mg, 0.154 mmol) were combined in a manner analogous to Example 77 to yield 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-N-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridin-2-amine (28 mg, 42%) as a beige solid. The material was purified via trituration with methanol. MP=241° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.37 (s, 1H), 8.03 (d, J=8.1 Hz, 2H), 7.51-7.67 (m, 6H), 7.17 (d, J=6.4 Hz, 1H), 6.85 (d, J=8.6 Hz, 2H), 3.80 (s, 2H), 3.69 (s, 3H), 3.15 (br s, 4H), 2.92 (br s, 4H). MS=464 (MH)+.

Sources & evidence

ORD record
ord-35542ccb3ef74840b1b4555a4261187b
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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