1-(2-Hydroxyethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → 1-(4-(6-(5-Fluoro-2-(methylthio)phenyl)-2-(methylthio)pyrimidin-4-yl)phenyl)-3-(2-hydroxyethyl)urea

HRID 1771568Notes

Reaction equation

HRID 1771568 reaction equation
FC1C=C(C2N=C(SC)N=C(N3CCOC[C@@H]3C)C=2)C=NC=1.Cl[C:24]1[CH:29]=[C:28]([C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[S:37][CH3:38])[N:27]=[C:26]([S:39][CH3:40])[N:25]=1.[OH:41][CH2:42][CH2:43][NH:44][C:45]([NH:47][C:48]1[CH:53]=[CH:52][C:51](B2OC(C)(C)C(C)(C)O2)=[CH:50][CH:49]=1)=[O:46]>>[F:36][C:34]1[CH:33]=[CH:32][C:31]([S:37][CH3:38])=[C:30]([C:28]2[N:27]=[C:26]([S:39][CH3:40])[N:25]=[C:24]([C:51]3[CH:52]=[CH:53][C:48]([NH:47][C:45]([NH:44][CH2:43][CH2:42][OH:41])=[O:46])=[CH:49][CH:50]=3)[CH:29]=2)[CH:35]=1

Participants

4

Reactant 3

HCID 446073541-(2-Hydroxyethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 67382782(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholineHCID 866911544-Chloro-6-(5-fluoro-2-(methylthio)phenyl)-2-(methylthio)pyrimidine

Product 1

HCID 673823711-(4-(6-(5-Fluoro-2-(methylthio)phenyl)-2-(methylthio)pyrimidin-4-yl)phenyl)-3-(2-hydroxyethyl)urea

Procedure

Method as described for intermediate 5 using 4-chloro-6-(5-fluoro-2-(methylthio)phenyl)-2-(methylthio)pyrimidine and 1-(2-hydroxyethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 18). Reaction mixture was partitioned between DCM and water, the organic phase passed through a PTFE hydrophobic frit and the solvent removed in vacuo. The residue was purified further by flash chromatography (40-100% EtOAc in petroleum ether (40:60) followed by 0-15% MeOH in petroleum ether (40:60) to afford 1-(4-(6-(5-fluoro-2-(methylthio)phenyl)-2-(methylthio)pyrimidin-4-yl)phenyl)-3-(2-hydroxyethyl)urea as a brown solid, (200 mg, 54%).

Workup

  1. customReaction mixture
  2. customwas partitioned between DCM and water
  3. customthe solvent removed in vacuo
  4. customThe residue was purified further by flash chromatography (40-100% EtOAc in petroleum ether (40:60)

Sources & evidence

ORD record
ord-30314599b5bf4576a25bf8634b11b968
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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