1-(2-Hydroxyethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → (S)-1-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-(2-hydroxyethyl)urea

HRID 1771555Notes

Reaction equation

HRID 1771555 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]([CH3:40])(=[O:39])=[O:38])[N:27]=[C:26]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][C@@H:42]2[CH3:47])[N:25]=1.[OH:48][CH2:49][CH2:50][NH:51][C:52]([NH:54][C:55]1[CH:60]=[CH:59][C:58](B2OC(C)(C)C(C)(C)O2)=[CH:57][CH:56]=1)=[O:53]>>[F:36][C:34]1[CH:33]=[CH:32][C:31]([S:37]([CH3:40])(=[O:39])=[O:38])=[C:30]([C:28]2[N:27]=[C:26]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][C@@H:42]3[CH3:47])[N:25]=[C:24]([C:58]3[CH:59]=[CH:60][C:55]([NH:54][C:52]([NH:51][CH2:50][CH2:49][OH:48])=[O:53])=[CH:56][CH:57]=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 86691148(S)-4-(4-chloro-6-(5-fluoro-2-(methylsulfonyl)phenyl)pyrimidin-2-yl)-3-methylmorpholine2×

Product 1

HCID 53359053(S)-1-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-(2-hydroxyethyl)ureaYield 24%

Procedure

Method as described for intermediate 5 using (S)-4-(4-chloro-6-(5-fluoro-2-(methylsulfonyl)phenyl)pyrimidin-2-yl)-3-methylmorpholine (intermediate 16) and 1-(2-hydroxyethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 18). Material was purified by prep HPLC (low pH) to afford a brown solid. Further purification was achieved using flash chromatography (20-100% EtOAc in petroleum ether (40:60) to afford a light brown solid (60 mg, 24%).

Workup

  1. customMaterial was purified by prep HPLC (low pH)
  2. customto afford a brown solid
  3. customFurther purification

Sources & evidence

ORD record
ord-e2c9b1e8aeee46489560d1eec5034eb7
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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