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

HRID 445221노트

반응식

HRID 445221 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 702Ethanol용매HCID 6342Acetonitrile용매

반응 조건

온도
85 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7bc79f7573b442bc96ef541f241ff276
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476300B2

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