Diisopropylethylamine → Ethyl 4-([2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl}-amino)-butanoate

HRID 2173749Notes

Reaction equation

[OH:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:6]=[C:5]([CH2:21][OH:22])[N:4]=1.I[CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33].C(N(C(C)C)CC)(C)C>C(#N)C>[OH:22][CH2:21][C:5]1[CH:6]=[C:7]([O:9][CH2:10][CH2:11][N:12]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])[CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]=[C:3]([CH2:2][OH:1])[N:4]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 180 mg of ethyl 4-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-butanoate in 18 ml of acetonitrile was added 207 mg of 1-iodo-2-[2-(2-methoxy-ethoxy)-ethoxy]-ethane and 192 μl of diisopropylethylamine. The mixture was heated for 3 days at 80° C. and then concentrated under reduced pressure and purified by flash chromatography on silica (Merck SuperVarioFlash 15 g column, Si60 15-40 μm), using a DCM/MeOH/water mixture (40/5/0.5). The fractions containing the desired product were combined and concentrated under reduced pressure. 51 mg of ethyl 4-([2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl}-amino)-butanoate were obtained. LC/MS (B): tr=0.70 min; [M+H]+: m/z 459.

Workup

concentrationconcentrated under reduced pressure
custompurified by flash chromatography on silica (Merck SuperVarioFlash 15 g column, Si60 15-40 μm)
additionThe fractions containing the desired product
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-c20f36d84dd546a6b24d5d1e85faee39
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056914B2

Reaction notes

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