Lithium Chloride → 6-(3-fluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

HRID 1676394노트

반응식

HRID 1676394 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:19]2[C:24](=[O:25])[N:23]3[CH2:26][CH2:27][N:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:22]3=[N:21][CH:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[N:35]1([C:41]([C:43]2[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=2)=[O:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:19]2[C:24](=[O:25])[N:23]3[CH2:26][CH2:27][N:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:22]3=[N:21][CH:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:46]3[CH:45]=[CH:44][C:43]([C:41]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)=[O:42])=[CH:48][CH:47]=3)[S:17][C:10]=12

참가 물질

7

반응물 3

HCID 433294Lithium ChlorideHCID 2773546[4-(Morpholine-4-carbonyl)phenyl]boronic acidHCID 673468456-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

생성물 1

HCID 589494336-(3-fluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A suspension of 6-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one (0.035 g, 0.060 mmol), 4-(morpholine-4-carbonyl)phenylboronic acid (0.017 g, 0.0721 mmol), Pd(PPh3)4 (0.003 g, 0.003 mmol) and lithium chloride (0.010 g, 0.240 mmol) in dioxane (1 mL) and 2M aqueous Na2CO3 (1 mL) was stirred at 100° C. for 50 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 20:1 CH2Cl2/MeOH. The product was obtained (23 mg; 59%) as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ 8.51 (d, 1H), 8.01 (s, 1H), 7.85-7.79 (m, 3H), 7.73-7.65 (m, 3H), 7.55-7.49 (m, 3H), 7.46 (m, 2H), 7.30 (m, 1H), 7.22, (m, 1H), 6.59 (dd, 1H), 4.33 (m, 4H), 3.95-3.36 (m, 8H). LRMS (APCI pos) m/e 646 (M+1).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 20:1 CH2Cl2/MeOH
  10. customThe product was obtained (23 mg; 59%) as a pale yellow solid

출처 및 근거

ORD 기록
ord-0dfd60134ea24936851dc08d73233353
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003662B2

반응 노트

불러오는 중…