Triphenylphosphine → 6-((5-(3,4-dichlorophenylamino)pyrazin-2-yl)methoxy)quinolin-2(1H)-one

HRID 77474

반응식

HRID 77474 반응식
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O.[OH:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38](=[O:43])[CH:37]=[CH:36]2.[Cl:44][C:45]1[CH:46]=[C:47]([NH:52][C:53]2[N:54]=[CH:55][C:56]([CH2:59]O)=[N:57][CH:58]=2)[CH:48]=[CH:49][C:50]=1[Cl:51]>C1COCC1>[Cl:44][C:45]1[CH:46]=[C:47]([NH:52][C:53]2[N:54]=[CH:55][C:56]([CH2:59][O:32][C:33]3[CH:34]=[C:35]4[C:40](=[CH:41][CH:42]=3)[NH:39][C:38](=[O:43])[CH:37]=[CH:36]4)=[N:57][CH:58]=2)[CH:48]=[CH:49][C:50]=1[Cl:51]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 1770652,6-DihydroxyquinolineHCID 5462977Diethyl azodicarboxylateHCID 86679762(5-(3,4-Dichlorophenylamino)pyrazin-2-yl)methanol

생성물 1

HCID 866797636-((5-(3,4-dichlorophenylamino)pyrazin-2-yl)methoxy)quinolin-2(1H)-one수율 13.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of Ph3P (0.07 g, 0.267 mmol) in THF (1.7 mL) was cooled to 0° C. under N2 and DEAD (0.076 ml, 0.481 mmol) was added dropwise. The mixture was stirred for 10 min, then 6-hydroxyquinolin-2(1H)-one (0.072 g, 0.444 mmol) was added. After stirring for 5 min, a solution of (5-((3,4-dichlorophenyl)amino)pyrazin-2-yl)methanol (0.1 g, 0.370 mmol) in THF (2 mL) was added. The reaction was stirred at room temperature overnight. The mixture was concentrated and partially purified by flash chromatography on silica gel using 30-100% ethyl acetate in hexanes, then 5-10% methanol in ethyl acetate. The desired fractions were concentrated to a solid, which was redissolved in DMF. Water was added to the vigorously stirred solution until a suspension formed. After stirring 18 h, the off-white solid was filtered, washed with methanol, and dried to yield 6-((5-(3,4-dichlorophenylamino)pyrazin-2-yl)methoxy)quinolin-2(1H)-one (0.02 g, 13%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.67 (1H, s), 9.97 (1H, s), 8.40 (1H, d, J=1.00 Hz), 8.28 (1H, d, J=1.51 Hz), 8.20 (1H, d, J=2.26 Hz), 7.86 (1H, d, J=9.79 Hz), 7.49-7.64 (2H, m), 7.37 (1H, s), 7.17-7.32 (2H, m), 6.51 (1H, dd, J=9.54, 2.01 Hz), 5.12 (2H, s). LCMS: R.T.=4.09; [M+H]+=412.93.

후처리

  1. stirringAfter stirring for 5 min
  2. stirringThe reaction was stirred at room temperature overnight
  3. concentrationThe mixture was concentrated
  4. custompartially purified by flash chromatography on silica gel using 30-100% ethyl acetate in hexanes
  5. concentrationThe desired fractions were concentrated to a solid, which
  6. dissolutionwas redissolved in DMF
  7. additionWater was added to the vigorously stirred solution until a suspension
  8. customformed
  9. stirringAfter stirring 18 h
  10. filtrationthe off-white solid was filtered
  11. washwashed with methanol
  12. customdried

출처 및 근거

ORD 기록
ord-d2ebce69e772453cafd8eeb9ecf3dafe
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841301B2

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