Cesium carbonate → HCID 178509957, compound

HRID 1157412Notes

Reaction equation

HRID 1157412 reaction equation
ClC1C=C(C=C(OC2C=C(O)C=CC=2Cl)C=1)C#N.C([O-])([O-])=O.[Cs+].[Cs+].BrCC1C2C(=NC(F)=CC=2)N(C(OC(C)(C)C)=O)N=1.[Cl:44][C:45]1[CH:46]=[C:47]([CH:50]=[C:51]([O:53][C:54]2[CH:59]=[C:58]([O:60][CH2:61][C:62]3[C:70]4[C:65](=[N:66][C:67]([F:71])=[CH:68][CH:69]=4)[N:64](C(OC(C)(C)C)=O)[N:63]=3)[CH:57]=[CH:56][C:55]=2[Cl:79])[CH:52]=1)[C:48]#[N:49]>C(O)(C(F)(F)F)=O>[Cl:44][C:45]1[CH:46]=[C:47]([CH:50]=[C:51]([O:53][C:54]2[CH:59]=[C:58]([O:60][CH2:61][C:62]3[C:70]4[C:65](=[N:66][C:67]([F:71])=[CH:68][CH:69]=4)[NH:64][N:63]=3)[CH:57]=[CH:56][C:55]=2[Cl:79])[CH:52]=1)[C:48]#[N:49]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 251318873-Chloro-5-(2-chloro-5-hydroxyphenoxy)benzonitrileHCID 25132591tert-butyl 3-(bromomethyl)-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylateHCID 251325923-chloro-5-{2-chloro-5-[(1-t-butyloxycarbonyl-6-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)methoxy]phenoxy}benzonitrile

Product 1

HCID 178509957HCID 178509957, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

In a manner identical to that described above for the synthesis of 1-2, from 2.97 g (10.68 mmol) of 3-chloro-5-(2-chloro-5-hydroxyphenoxy)benzonitrile (C-3), 3.29 g (10.15 mmol) of Cs2CO3, and 3.34 g (10.15 mmol) of tert-butyl 3-(bromomethyl)-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (37-5) was prepared crude 3-chloro-5-{2-chloro-5-[(1-t-butyloxycarbonyl-6-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)methoxy]phenoxy}benzonitrile (37-6) as an oil. This BOC-protected material (3.66 g) was immediately dissolved in 10 mL TFA, and the resulting solution stirred for 20 minutes at room temperature. The crude reaction mixture was concentrated in vacuo and purified via silica gel chromatography (10-70% EtOAc/hexane) to yield the title compound. H1 NMR (CDCl3): 5.47 (s, 2H), 6.85 (d, 1H), 6.95 (d, 1H), 7.02 (s, 1H), 7.10 (s, 1H), 7.30 (s, 1H), 7.40 (d, 1H), 8.38 (t, 1H), 11.38 (bs, 1H).

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated in vacuo
  3. custompurified via silica gel chromatography (10-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-7695af9487f049588ec4c607b597d5d2
Source dataset
uspto-grants-2010_10
Patent number
US07807684B2

Reaction notes

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