1,2-Dimethoxyethane → N-(6-Fluoro-2-Methyl-3-{5-[(5-Methyl-4,5,6,7-Tetrahydropyrazolo[1,5-A]pyrazin-2-Yl)amino]-6-Oxo-1,6-Dihydropyridazin-3-Yl}phenyl)-1-Benzothiophene-2-Carboxamide

HRID 1907793ノート

反応式

HRID 1907793 の反応式
Cl[C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:19]=[C:13]3[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]3[N:11]=2)[C:5](=[O:8])[NH:6][N:7]=1.[F:20][C:21]1[C:26]([NH:27][C:28]([C:30]2[S:34][C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[CH:31]=2)=[O:29])=[C:25]([CH3:39])[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1.COCCOC.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.O.C(OCC)(=O)C>[F:20][C:21]1[C:26]([NH:27][C:28]([C:30]2[S:34][C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[CH:31]=2)=[O:29])=[C:25]([CH3:39])[C:24]([C:2]2[CH:3]=[C:4]([NH:9][C:10]3[CH:19]=[C:13]4[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]4[N:11]=3)[C:5](=[O:8])[NH:6][N:7]=2)=[CH:23][CH:22]=1

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 58540259N-(6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzo[b]thiophene-2-carboxamideHCID 585403166-chloro-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one

生成物 1

HCID 58540422N-(6-Fluoro-2-Methyl-3-{5-[(5-Methyl-4,5,6,7-Tetrahydropyrazolo[1,5-A]pyrazin-2-Yl)amino]-6-Oxo-1,6-Dihydropyridazin-3-Yl}phenyl)-1-Benzothiophene-2-Carboxamide収率 49.8%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A microwave tube equipped with a magnetic stirrer was charged with 6-chloro-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one (225 mg, 0.80 mmol), N-(6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzo[b]thiophene-2-carboxamide (463 mg, 1.13 mmol), DME (5 mL) and 1M aqueous sodium carbonate (2 mL). After bubbling Argon while sonicating for 30 sec, Pd(PPh3)4 (65 mg, 0.06 mmol) was added. The mixture was subjected to microwave irradiation at 150° C. for 20 min. After this time, ethyl acetate (10 mL) and water (10 mL) were added. The separated aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organics were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford the title compound N-{6-fluoro-2-methyl-3-[5-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridazin-3-yl]phenyl}-1-benzothiophene-2-carboxamide (211 mg) in 50% yield.

後処理

  1. customA microwave tube equipped with a magnetic stirrer
  2. customAfter bubbling Argon
  3. customwhile sonicating for 30 sec
  4. customirradiation at 150° C. for 20 min
  5. extractionThe separated aqueous layer was extracted with ethyl acetate (2×10 mL)
  6. washThe combined organics were washed with brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by column chromatography

出典と根拠

ORDレコード
ord-2a132d1941af4b86823e3072006c1713
出典データセット
uspto-grants-2013_12
特許番号
US08598174B2

反応ノート

読み込み中…