Cesium carbonate → 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-2,6-dimethyl-8-(1-propyl-butyl)-imidazo[1,2-b]pyridazine

HRID 1432678ノート

反応式

HRID 1432678 の反応式
I[C:2]1[N:6]2[N:7]=[C:8]([CH3:18])[CH:9]=[C:10]([CH:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])[C:5]2=[N:4][C:3]=1[CH3:19].[Cl:20][C:21]1[N:22]=[C:23]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[S:24][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CN(C=O)C>[Cl:20][C:21]1[N:22]=[C:23]([N:26]2[CH2:27][CH2:28][O:29][CH2:30][CH2:31]2)[S:24][C:25]=1[C:2]1[N:6]2[N:7]=[C:8]([CH3:18])[CH:9]=[C:10]([CH:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])[C:5]2=[N:4][C:3]=1[CH3:19]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 534400954-(4-Chlorothiazol-2-YL)morpholineHCID 579329063-Iodo-2,6-dimethyl-8-(1-propyl-butyl)-imidazo[1,2-b]pyridazine

生成物 1

HCID 579330703-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-2,6-dimethyl-8-(1-propyl-butyl)-imidazo[1,2-b]pyridazine

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
130 °C

実験手順

A 15 mL round bottom flask is charged with 3-iodo-2,6-dimethyl-8-(1-propyl-butyl)-imidazo[1,2-b]pyridazine (0.200 g, 0.000539 moles), 4-(4-chloro-thiazol-2-yl)-morpholine (0.165 g, 0.000808 moles), Cs2CO3 (0.361 g, 0.00108 moles, 2.0 equiv), Pd(dba)2 (0.0092 g, 0.0000161 moles, 0.03 equiv), PPh3 (0.00847 gram, 0.000323 moles, 0.060 equiv) and DMF (2.0 mL). Nitrogen is bubbled through the reaction mixture for 15 minutes; then, the reaction mixture is heated at 130° C. overnight. The next day, the reaction mixture is partitioned between Et2O and a saturated solution of NH4Cl. The aqueous layer is extracted twice more with Et2O. The organic extracts are combined, washed 2-3 times with H2O, washed once with brine, and dried over Na2SO4. The solvents are evaporated in vacuo and the crude reaction mixture is purified via silica gel chromatography. Yield=0.1737 g (72%). 1H-NMR (CDCl3), δ 0.87 (t, J=7 Hz, 6H), 1.14-1.37 (m, 4H), 1.74 (q, J=8 Hz, 4H), 2.54 (s, 3H), 2.50 (s, 3H), 3.48 (m, 1H), 3.53 (t, J=5 Hz, 4H), 3.83 (t, J=5 Hz, 4H), 6.71 (br s, 1H) ppm. LC/MS (m/z): calcd. for C22H30ClN5OS (M+H)+: 448; found: 448.

後処理

  1. customNitrogen is bubbled through the reaction mixture for 15 minutes
  2. customThe next day, the reaction mixture is partitioned between Et2O
  3. extractionThe aqueous layer is extracted twice more with Et2O
  4. washwashed 2-3 times with H2O
  5. washwashed once with brine
  6. dry with materialdried over Na2SO4
  7. customThe solvents are evaporated in vacuo
  8. customthe crude reaction mixture
  9. customis purified via silica gel chromatography

出典と根拠

ORDレコード
ord-70f8952ef06148bcb87cbd7b286abbdb
出典データセット
uspto-grants-2009_11
特許番号
US07612067B2

反応ノート

読み込み中…