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 1676394ノート

反応式

HRID 1676394 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 10340Sodium Carbonate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-0dfd60134ea24936851dc08d73233353
出典データセット
uspto-grants-2011_08
特許番号
US08003662B2

反応ノート

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