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

HRID 445221ノート

反応式

HRID 445221 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 702Ethanol溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
85 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7bc79f7573b442bc96ef541f241ff276
出典データセット
uspto-grants-2013_07
特許番号
US08476300B2

反応ノート

読み込み中…