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

HRID 1771574Notes

Reaction equation

HRID 1771574 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12](SC)[N:11]=[C:10]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]3[CH3:22])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.ClC1N=C(N2CCOC[C@@H]2C)C=C(C2C=NC=C(F)C=2)N=1.[F:44][C:45]1[CH:46]=[C:47]([NH:60][C:61]([NH:63][CH2:64][CH2:65][F:66])=[O:62])[CH:48]=[CH:49][C:50]=1B1OC(C)(C)C(C)(C)O1>>[F:44][C:45]1[CH:46]=[C:47]([NH:60][C:61]([NH:63][CH2:64][CH2:65][F:66])=[O:62])[CH:48]=[CH:49][C:50]=1[C:12]1[N:13]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH:9]=[C:10]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]2[CH3:22])[N:11]=1

Participants

4

Reactant 3

HCID 67382782(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholineHCID 86663172N-(2-Fluoroethyl)-N′-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea2×HCID 86691143(S)-4-(2-chloro-6-(5-fluoropyridin-3-yl)pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 53379862(S)-1-(3-fluoro-4-(4-(5-fluoropyridin-3-yl)-6-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)urea

Procedure

Method as described for intermediate 5 using(S)-4-(2-chloro-6-(5-fluoropyridin-3-yl)pyrimidin-4-yl)-3-methylmorpholine (intermediate 7) and 1-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-fluoroethyl)urea (intermediate 14). Material was purified by prep HPLC (high pH) followed by purification using a TsOH cartridge (500 mg) to afford a brown solid, (10 mg, 6%).

Workup

  1. customMaterial was purified by prep HPLC (high pH)
  2. customfollowed by purification
  3. customto afford a brown solid, (10 mg, 6%)

Sources & evidence

ORD record
ord-7db7369aa7684d69a391ce0da87d7976
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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