Diisopropylethylamine → Methyl 3-([2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl}-amino)-propanoate

HRID 2173756Notes

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][C:15]([O:17][CH3:18])=[O:16])[CH:6]=[C:5]([CH2:19][OH:20])[N:4]=1.I[CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31].C(N(C(C)C)CC)(C)C>C(#N)C>[OH:20][CH2:19][C:5]1[CH:6]=[C:7]([O:9][CH2:10][CH2:11][N:12]([CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:8]=[C:3]([CH2:2][OH:1])[N:4]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 284 mg of methyl 3-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-propanoate in 28 ml of acetonitrile was added 356 mg of 1-iodo-2-[2-(2-methoxy-ethoxy)-ethoxy]-ethane and 330 μl of diisopropylethylamine. The mixture was heated at 80° C. for 3 days and then concentrated under reduced pressure and purified by flash chromatography on silica (Analogix Super Flash SiO2 SF25-40g), using a gradient of 5 to 10% MeOH in DCM. The fractions containing the desired product were combined and concentrated under reduced pressure. 165 mg of methyl 3-([2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl}-amino)-propanoate were obtained. LC/MS (B): tr=0.44 min; [M+H]+: m/z 431.

Workup

concentrationconcentrated under reduced pressure
custompurified by flash chromatography on silica (Analogix Super Flash SiO2 SF25-40g)
additionThe fractions containing the desired product
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-e4e8e760d8134774b36766d0a4cf414b
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056914B2

Reaction notes

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