Triethylamine → Isoquinoline,6-[[1-(2-pyrimidinyl)-4-piperidinyl]oxy]-,hydrochloride

HRID 1022879Notes

Reaction equation

Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[N:14][CH:13]=[CH:12]3)[CH2:4][CH2:3]1.C(N(CC)CC)C.[Cl:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][N:28]=1>N1C=CC=CC=1>[ClH:26].[N:28]1[CH:27]=[CH:32][CH:31]=[N:30][C:29]=1[N:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[N:14][CH:13]=[CH:12]3)[CH2:4][CH2:3]1

Participants

Conditions

Temperature: 65 °C

Procedure

150 mg of 6-(Piperidine-4-yloxy)-isoquinoline hydrochloride (124) are dissolved in 10 mL of dry pyridine. 177 mg of triethylamine and 69 mg of 4-chloropyrimidine are added and the solution is stirred at 65° C. for 6 hours. The reaction mixture is poured on brine and extracted three times with ethyl acetate. The combined organic layers are dried over magnesium sulfate, evaporated to dryness and the crude product is purified by preparative HPLC. The product is converted into the corresponding HCl salt by taking up the product in 20 mL of 1 N hydrochloric acid followed by lyophilization. Yield: 47 mg. Rt=1.05 min (Method #2). Detected mass: 307.1 (M+H+).

Workup

additionThe reaction mixture is poured on brine
extractionextracted three times with ethyl acetate
dry with materialThe combined organic layers are dried over magnesium sulfate
customevaporated to dryness
customthe crude product is purified by preparative HPLC

Sources & evidence

ORD record: ord-d47123567d324623a5ee642e8f611206
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722671B2

Reaction notes

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