Ethylene Glycol → 2-Pyridin-2-yl-ethanesulfonic acid [6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide

HRID 8615Notes

Reaction equation

HRID 8615 reaction equation
[H-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].Cl[C:8]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)[N:11]=[C:10]([NH:20][S:21]([CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)(=[O:23])=[O:22])[C:9]=1[O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:39][CH3:40].Cl>CN(C=O)C>[OH:5][CH2:4][CH2:3][O:6][C:8]1[N:13]=[C:12]([C:14]2[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=2)[N:11]=[C:10]([NH:20][S:21]([CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)(=[O:23])=[O:22])[C:9]=1[O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:39][CH3:40]

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 865924742-Pyridin-2-yl-ethanesulfonic acid [6-chloro-5-(2-methoxyphenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide

Product 1

HCID 235482542-Pyridin-2-yl-ethanesulfonic acid [6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of NaH (701 mg, 60% in mineral oil) in DMF (15 ml) was added ethylene glycol (15 ml). After the evolution of gas had ceased, 2-pyridin-2-yl-ethanesulfonic acid [6-chloro-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide (800 mg) was added and the resulting solution was stirred at 90° C. for 40 h. The solution was neutralised with 2 N aq. HCl (7 ml) before it was evaporated. The brown residue was purified by chromatography on prep. tlc-plates with EA:methanol:sat. aq. ammonia 10:2:1. The product was further purified by crystallisation from methanol:diethyl ether:pentane to give 2-pyridin-2-yl-ethanesulfonic acid [6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide (280 mg) as beige crystals. 1H-NMR(300 MHz, CDC3): 3.36–3.43(m, 2H), 3.86–3.90(m, 2H), 3.94(s, 3H), 4.23–4.30(m, 2H), 4.564.62(m, 2H), 6.91(dt, Jd=1.5, Jt=7.7, 1H, 7.00(dd, J=1.7, 8.2, 1H, 7.08–7.20(m, 4H), 7.57(dt, Jd=1.8, Jt=7.9, 1H), 8.15(dd, J=1.7, 4.6, 2H), 8.43(d, J=4.4, 1H), 8.72(dd, J=1.7, 4.6, 2H); LC-MS: tR=3.23 min, [M+1]+=524.48, [M−1]−=522.25.

Workup

  1. customwas evaporated
  2. customThe brown residue was purified by chromatography on prep
  3. customThe product was further purified by crystallisation from methanol

Sources & evidence

ORD record
ord-e28236ae2b274d9c96885e7fe9ca69d9
Source dataset
uspto-grants-2006_08
Patent number
US07091201B2

Reaction notes

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