Cesium fluoride → 3-(6-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl)thiophene-2-carbonitrile

HRID 445221Notes

Reaction equation

HRID 445221 reaction equation
Br[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]#[N:8].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].Cl.[OH:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([O:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]3)=[CH:45][CH:44]=1)=[C:37](B(O)O)[CH:36]=[CH:35]2>C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[OH:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([O:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH2:50][CH2:51][N:52]3[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]3)=[CH:45][CH:44]=1)=[C:37]([C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]#[N:8])[CH:36]=[CH:35]2

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 27400883-Bromothiophene-2-carbonitrileHCID 673086676-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ylboronic acid hydrochloride

Product 1

HCID 583385773-(6-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl)thiophene-2-carbonitrileYield 10%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

Add 3-bromothiophene-2-carbonitrile (93 mg, 494.6 μmol), palladium (II) acetate (12 mg, 53.4 μmol), tricyclohexylphosphine (21 mg, 74.9 μmol), cesium fluoride (336 mg, 2.2 mmol) to a solution of 6-hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ylboronic acid hydrochloride (100 mg, 245.5 μmol) in ethanol (2 mL), and acetonitrile (8 mL). Purge the reaction vessel 3 times with nitrogen. Stir the mixture at 85° C. for 2 hours. Cool the mixture and filter. Wash the resulting solids with acetonitrile. Concentrate the combined filtrate and washes. Purify the residue by DOWEX ion exchange resin to obtain the crude product. Purify the crude product by Prep-HPLC to obtain the title compound (12 mg, 24.55 μmol).

Workup

  1. customPurge the reaction vessel 3 times with nitrogen
  2. temperatureCool the mixture
  3. filtrationfilter
  4. washWash the resulting solids with acetonitrile
  5. concentrationConcentrate the combined filtrate and washes
  6. customPurify the residue by DOWEX ion exchange resin
  7. customto obtain the crude product
  8. customPurify the crude product by Prep-HPLC

Sources & evidence

ORD record
ord-7bc79f7573b442bc96ef541f241ff276
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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