8-Bromo-(1,2,4)triazolo(1,5-a)pyridin-2-amine → N-[3-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-phenyl]-N-methyl-methanesulfonamide

HRID 1889866Notes

Reaction equation

HRID 1889866 reaction equation
Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH2:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:12][N:13]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=1)[S:14]([CH3:17])(=[O:16])=[O:15]>>[NH2:11][C:9]1[N:10]=[C:3]2[C:2]([C:20]3[CH:19]=[C:18]([N:13]([CH3:12])[S:14]([CH3:17])(=[O:15])=[O:16])[CH:23]=[CH:22][CH:21]=3)=[CH:7][CH:6]=[CH:5][N:4]2[N:8]=1

Participants

3

Reactant 2

HCID 468640698-Bromo-(1,2,4)triazolo(1,5-a)pyridin-2-amineHCID 57416160N-Methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide

Product 1

HCID 67481389N-[3-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-phenyl]-N-methyl-methanesulfonamide

Procedure

A round bottom flask was charged with potassium carbonate (0.56 g, 4.0 mmol) and acetone (20 mL). To the suspension was added N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-methanesulfonamide (1.0 g, 3.4 mmol) followed by iodomethane (0.25 mL, 4.0 mmol). The mixture was stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane (20 mL), filtered through a plug of diatomaceous earth, rinsed with dichloromethane and evaporated to a viscous oil. The material was subjected to high vacuum for 18 hours. N-Methyl-N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-methanesulfonamide was isolated as pale yellow solid (1.03 g, 98%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.76-7.70 (m, 2H), 7.53 (d, J=7.9 Hz, 1H), 7.39 (t, J=7.5 Hz, 1H), 3.34 (s, 3H), 2.86 (s, 3H), 1.35 (s, 12H). MS=312 (MH)+. 127b) N-[3-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-phenyl]-N-methyl-methanesulfonamide was prepared from 8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (500.0 mg, 2.347 mmol) and N-methyl-N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-methanesulfonamide (800.0 mg, 2.571 mmol) in a manner analogous to Example 2c. Product isolated as a white foam (0.529 g, 71%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.57 (d, J=6.5 Hz, 1H), 8.13-8.10 (m, 1H), 8.07 (d, J=7.9 Hz, 1H), 7.75 (d, J=7.5 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 6.99 (t, J=6.9 Hz, 1H), 6.12 (s, 2H), 3.31 (s, 3H), 3.01 (s, 3H). MS=318 (MH)+. 127c) N-Methyl-N-(3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-yl}-phenyl)-methanesulfonamide was prepared from N-[3-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-phenyl]-N-methyl-methanesulfonamide (75.0 mg, 0.236 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (67.0 mg, 0.262 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a yellow foam (0.033 g, 28%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.41 (d, J=6.6, 1H), 8.13 (s, 3H), 7.93 (d, J=7.9 Hz, 1H), 7.59 (d, J=7.4 Hz, 1H), 7.56-7.45 (m, 3H), 7.44 (dd, J=8.2, 1.2 Hz, 1H), 6.98-6.92 (m, 3H), 6.64 (s, 1H), 3.42 (s, 3H), 3.19-3.14 (m, 4H), 2.89 (s, 3H), 2.63-2.57 (m, 4H), 2.36 (s, 3H). MS=492 (MH)+.

Sources & evidence

ORD record
ord-06aeddd995d045a7b5c73884bc44bd63
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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