Bromotrimethylsilane → 4-(4-Bromothiazolo[5,4-c]pyridin-2-yl)-3-chloro-5-fluorobenzonitrile

HRID 2366229Notes

Reaction equation

HRID 2366229 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:20])[C:9]=1[C:10]1[S:11][C:12]2[C:13](Cl)=[N:14][CH:15]=[CH:16][C:17]=2[N:18]=1)[C:5]#[N:6].C[Si]([Br:25])(C)C>C(#N)CC>[Br:25][C:13]1[C:12]2[S:11][C:10]([C:9]3[C:8]([F:20])=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=3[Cl:1])=[N:18][C:17]=2[CH:16]=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 76113Bromotrimethylsilane2×HCID 867233143-Chloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-5-fluorobenzonitrile

Product 1

HCID 867233154-(4-Bromothiazolo[5,4-c]pyridin-2-yl)-3-chloro-5-fluorobenzonitrileYield 101.7%

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Procedure

A suspension of 3-chloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-5-fluorobenzonitrile (0.077 g, 0.24 mmol) and trimethylsilyl bromide (63 μL 0.48 mmol) in propionitrile (2.4 mL) was heated under reflux for 5 hours before further trimethylsilyl bromide (30 μL, 0.24 mmol) was added. The resulting mixture was heated under reflux for a further 16 hours then partitioned between DCM and water. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the desired compound as an off-white solid (0.090 g, quant. yield). 1H NMR (300 MHz, CDCl3): δ 8.53 (d, J=5.6 Hz, 1H), 8.03 (d, J=5.6 Hz, 1H), 7.72 (t, J=1.4 Hz, 1H), 7.52 (dd, J=8.3; 1.5 Hz, 1H). LCMS (Method D): RT=3.89 min, m/z: 368 [M+H+].

Workup

  1. temperaturewas heated
  2. additionwas added
  3. temperatureThe resulting mixture was heated
  4. temperatureunder reflux for a further 16 hours
  5. customthen partitioned between DCM and water
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ca2360529c014756b15007c915f74f73
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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