2-Amino-3-Hydroxypyridine → HCID 67481450, compound

HRID 1890017Notes

Reaction equation

HRID 1890017 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[OH:9][C:10]1[C:11]([NH:16][C:17]([NH:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[S:18])=[N:12][CH:13]=[CH:14][CH:15]=1>>[OH:9][C:10]1[C:11]([NH:16][C:17]([NH:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[S:18])=[N:12][CH:13]=[CH:14][CH:15]=1.[NH2:16][C:11]1[N:1]=[C:2]2[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]2[N:12]=1

Participants

4

Reactant 2

HCID 281142-Amino-3-HydroxypyridineHCID 86648362HCID 86648362, compound

Product 2

HCID 67481450HCID 67481450, compoundHCID 86648362HCID 86648362, compound

Procedure

260 a)N-(3-Hydroxy-2-pyridinyl)-N′-carboethoxy-thiourea was prepared from 2-amino-pyridin-3-ol (4.00 g, 0.0363 mol) in a manner analogous to Example 2a. The product of the reaction was isolated as a yellow solid. 260 b) 2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-ol was prepared from N-(3-hydroxy-2-pyridinyl)-N′-carboethoxy-thiourea (1.8 g, 5.9 mmol) in a manner analogous to Example 2b. Product was isolated as a beige solid (3.17 g, 58%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.18 (bs, 1H), 8.02 (dd, J=6.41 Hz, 1.2 Hz, 1H), 6.71-6.64 (m, 2H), 5.79 (bs, 2H). MS=151.0 (MH)+. 260 c) 2-Amino-[1,2,4]triazolo[1,5-a]pyridin-8-ol (0.200 g, 1.33 mmol) was suspended in acetone (1.9 mL). 1-(bromomethyl)-3-chloro-benzene (0.184 mL, 1.40 mmol) and potassium carbonate (193 mg, 1.40 mmol) were added and the reaction mixture was heated to 80° C. for 1 hour. Reaction mixture was cooled to room temperature, diluted with water, extracted with dichloromethane, dried over magnesium sulfate, filtered, and concentrated. Resulting oil was taken up in dichloromethane and purified via chromatography (silica gel 0-100% ethyl acetate in hexanes). 8-(3-Chloro-benzyloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was isolated as an oil which solidified on standing. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.17 (d, J=6.6 Hz, 1H), 7.56 (s, 1H), 7.44-7.42 (m, 3H), 6.99 (d, J=7.9 Hz, 1H), 6.79-6.75 (m, 1H), 5.94 (bs, 2H), 5.30 (s, 2H). MS=275 (MH)+. 260 d) [8-(3-Chloro-benzyloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 8-(3-chloro-benzyloxy)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (95.0 mg, 0.346 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (102 mg, 0.399 mmol in a manner analogous to Example 2d. Product was isolated as a pale orange solid (0.073 g, 47%). MP=135-138° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.33 (s, 1H), 8.37 (d, J=6.7 Hz, 1H), 7.58 (s, 1H), 7.51-7.44 (m, 5H), 7.09 (d, J=7.9 Hz, 1H), 6.91-6.86 (m, 3H), 5.35 (s, 2H), 3.04-3.01 (m, 4H), 2.46-2.44 (m, 4H), 2.22 (s, 3H). MS=449 (MH)+.

Workup

  1. customThe product of the reaction was isolated as a yellow solid

Sources & evidence

ORD record
ord-e0b645c3f6ed498b86c3ea80e8e1776d
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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