Morpholine → 4-[5-Methyl-6-(2-methyl-6-morpholin-4-yl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 1174765Notes

Reaction equation

HRID 1174765 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([NH:21][C:22]3[C:23]([CH3:29])=[N:24][C:25](Cl)=[CH:26][CH:27]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([NH:21][C:22]3[C:23]([CH3:29])=[N:24][C:25]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[CH:26][CH:27]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 8083MorpholineHCID 112471394-[6-(6-Chloro-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

Product 1

HCID 598566544-[5-Methyl-6-(2-methyl-6-morpholin-4-yl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl EsterYield 58%

Procedure

A solution of 4-[6-(6-chloro-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (613 mg, 1.46 mmol) in 15 mL morpholine was reacted under microwave irradiation at 180° C. for 14 hours. Mixture was concentrated and purified by HPLC to give Compound A91 as a white solid (427 mg, 58%). 1H NMR (MeOH-d4, 400 MHz) δ 1.03-1.05 (d, 6H), 1.51-1.60 (m, 2H), 1.78-1.85 (m, 2H), 1.98 (s, 3H), 2.29 (s, 3H),3.19-3.25 (m, 2H), 3.54-3.58 (m, 6H), 3.65-3.67 (m, 4H), 4.65-4.70 (m, 1H), 5.20-5.25 (m, 1H), 7.08-7.10 (d, 1H), 7.68-7.71 (d, 1H), 8.07 (s, 1H). Exact mass calculated for C24H34N6O4 470.26, found 471.3 (MH+).

Workup

  1. concentrationMixture was concentrated
  2. custompurified by HPLC

Sources & evidence

ORD record
ord-15ee58d9d31f43ff9b869963aeb43442
Source dataset
uspto-grants-2010_11
Patent number
US07838525B2

Reaction notes

Loading…