(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholine → (S)-1-(2,2-difluoroethyl)-3-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)urea

HRID 1771559Notes

Reaction equation

HRID 1771559 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.[F:48][CH:49]([F:70])[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:48][CH:49]([F:70])[CH2:50][NH:51][C:52]([NH:54][C:55]1[CH:60]=[CH:59][C:58]([C:24]2[CH:29]=[C:28]([C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=3[S:37]([CH3:40])(=[O:39])=[O:38])[N:27]=[C:26]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][C@@H:42]3[CH3:47])[N:25]=2)=[CH:57][CH:56]=1)=[O:53]

Participants

4

Reactant 3

HCID 67382782(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholineHCID 866911471-(2,2-Difluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 86691148(S)-4-(4-chloro-6-(5-fluoro-2-(methylsulfonyl)phenyl)pyrimidin-2-yl)-3-methylmorpholine2×

Product 1

HCID 53379556(S)-1-(2,2-difluoroethyl)-3-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)ureaYield 23%

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-(2,2-difluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 20). Purification was achieved using flash chromatography (20-90% EtOAc in petroleum ether (40:60). The material was further purified by prep HPLC (low pH) to afford a white solid (20 mg, 23%).

Workup

  1. customPurification
  2. customThe material was further purified by prep HPLC (low pH)

Sources & evidence

ORD record
ord-01a068bd53404adfb052f0517fdeb141
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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