1-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → (S)-1-cyclopropyl-3-(3-fluoro-4-(4-(5-fluoropyridin-3-yl)-6-(3-methylmorpholino)pyrimidin-2-yl)phenyl)urea

HRID 1771570Notes

Reaction equation

HRID 1771570 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.[CH:44]1([NH:47][C:48]([NH:50][C:51]2[CH:56]=[CH:55][C:54](B3OC(C)(C)C(C)(C)O3)=[C:53]([F:66])[CH:52]=2)=[O:49])[CH2:46][CH2:45]1>>[CH:44]1([NH:47][C:48]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([C:12]3[N:13]=[C:8]([C:4]4[CH:5]=[N:6][CH:7]=[C:2]([F:1])[CH:3]=4)[CH:9]=[C:10]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]4[CH3:22])[N:11]=3)=[C:53]([F:66])[CH:52]=2)=[O:49])[CH2:46][CH2:45]1

Participants

4

Reactant 3

HCID 666792291-Cyclopropyl-3-(3-fluoro-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 86691143(S)-4-(2-chloro-6-(5-fluoropyridin-3-yl)pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 53379769(S)-1-cyclopropyl-3-(3-fluoro-4-(4-(5-fluoropyridin-3-yl)-6-(3-methylmorpholino)pyrimidin-2-yl)phenyl)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-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 11). Material was purified by prep HPLC twice (low pH) followed by purification using a TsOH cartridge (100 mg) to afford a yellow solid, (4.5 mg, 15%)

Workup

  1. customMaterial was purified by prep HPLC twice (low pH)
  2. customfollowed by purification
  3. customto afford a yellow solid, (4.5 mg, 15%)

Sources & evidence

ORD record
ord-4e3fdfd620f8482696571ef061d9a010
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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