Diisopropylamine → 9-Cyclopropyl-6-fluoro-7-(2-(pyridin-2-YL)ethynyl)isothiazolo[5,4-B]quinoline-3,4(2H,9H)-dione

HRID 1640962ノート

反応式

HRID 1640962 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[C:7]3[C:17](=[O:18])[NH:16][S:15][C:8]=3[N:9]2[CH:12]2[CH2:14][CH2:13]2)=[CH:4][C:3]=1[F:20].[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)#[CH:22].C(NC(C)C)(C)C>CN(C=O)C.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>[CH:12]1([N:9]2[C:10]3[C:5](=[CH:4][C:3]([F:20])=[C:2]([C:22]#[C:21][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[CH:11]=3)[C:6](=[O:19])[C:7]3[C:17](=[O:18])[NH:16][S:15][C:8]2=3)[CH2:14][CH2:13]1

参加物

6

反応物 3

HCID 7912DiisopropylamineHCID 137268EthynylpyridineHCID 599995297-Bromo-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-B]quinoline-3,4-dione

生成物 1

HCID 599995409-Cyclopropyl-6-fluoro-7-(2-(pyridin-2-YL)ethynyl)isothiazolo[5,4-B]quinoline-3,4(2H,9H)-dione

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

Pd (PPh3)4 (4.5 mg) is added to a stirred solution of 7-bromo-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione (23 mg, 0.065 mmole) in DMF (1 mL), followed by the addition of 2-ethynylpyridine (2 equivalents, 0.13 mmole) and diisopropyl amine (0.15 mL.) under argon at room temperature. The reaction tube is sealed and then stirred in a microwave (100 W, 90° C.) until complete as monitored by LC/MS. The reaction mixture is filtered and the filtrate concentrated in vacuo. The residue is dissolved in a mixture of DMF: CHCl3: MeOH (1:8:1) and precipitated by adding diethyl ether (1-2 ml). This process is repeated three to five times. The resulting solid, 9-cyclopropyl-6-fluoro-7-(2-(pyridin-2-yl)ethynyl) isothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione, is washed with water to remove salt. The product is dried and analyzed. HPLC may be needed to obtain adequately pure product.

後処理

  1. customThe reaction tube is sealed
  2. filtrationThe reaction mixture is filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. dissolutionThe residue is dissolved in a mixture of DMF: CHCl3: MeOH (1:8:1)
  5. customprecipitated
  6. additionby adding diethyl ether (1-2 ml)
  7. washThe resulting solid, 9-cyclopropyl-6-fluoro-7-(2-(pyridin-2-yl)ethynyl) isothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione, is washed with water
  8. customto remove salt
  9. customThe product is dried
  10. customto obtain adequately pure product

出典と根拠

ORDレコード
ord-013897ccd0e64d0e97ae90be98156117
出典データセット
uspto-grants-2012_02
特許番号
US08114888B2

反応ノート

読み込み中…