Diisopropylethylamine → 8-Fluoro-4-(2-methylaminoethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

HRID 558960ノート

反応式

HRID 558960 の反応式
Cl.CN.[CH3:4][C:5]1[CH:29]=[C:28]([C:30]([N:32]2[CH2:38][CH2:37][CH2:36][CH2:35][C:34]3[CH:39]=[CH:40][CH:41]=[CH:42][C:33]2=3)=[O:31])[CH:27]=[CH:26][C:6]=1[CH2:7][NH:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][C:19]=2[F:21])[N:14]([CH2:22][CH:23]=O)[C:13](=[O:25])[CH2:12]1)=[O:10].[CH:43]([N:46](C(C)C)CC)(C)C.C([BH3-])#N.[Na+]>CO.C1(C)C=CC=CC=1.C(O)(=O)C>[CH3:4][C:5]1[CH:29]=[C:28]([C:30]([N:32]2[CH2:38][CH2:37][CH2:36][CH2:35][C:34]3[CH:39]=[CH:40][CH:41]=[CH:42][C:33]2=3)=[O:31])[CH:27]=[CH:26][C:6]=1[CH2:7][NH:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][C:19]=2[F:21])[N:14]([CH2:22][CH2:23][NH:46][CH3:43])[C:13](=[O:25])[CH2:12]1)=[O:10]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 6364545Methylamine hydrochlorideHCID 115338268-Fluoro-3-oxo-4-(2-oxoethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

生成物 1

HCID 116783198-Fluoro-4-(2-methylaminoethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 887Methanol溶媒HCID 1140Toluene溶媒

実験手順

Methylamine hydrochloride (68 mg, 1.0 mmol) was added to a solution of 8-fluoro-3-oxo-4-(2-oxoethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide from Example 10 (53 mg, 0.1 mmol) in methanol (4.0 ml) then the mixture was cooled in an ice/water bath. Diisopropylethylamine (185 μl, 1.0 mmol) was added and the mixture was stirred for 20 mins. Acetic acid (0.40 ml) and sodium cyanoborohydride (6.3 mg, 0.1 mmol) were added and the mixture was allowed to warm to room temperature. The mixture was stirred for 3 h, diluted with toluene and evaporated in vacuo. The residue was partitioned between EtOAc and saturated sodium hydrogen carbonate solution and separated. The organic phase was washed with brine, dried and evaporated in vacuo. The residue was purified by flash chromatography on silica (eluant dichloromethane:methanol:triethylamine 95:4:1) to give a white solid; yield 22 mg, 41%.

後処理

  1. temperaturethe mixture was cooled in an ice/water bath
  2. stirringThe mixture was stirred for 3 h
  3. customevaporated in vacuo
  4. customThe residue was partitioned between EtOAc and saturated sodium hydrogen carbonate solution
  5. customseparated
  6. washThe organic phase was washed with brine
  7. customdried
  8. customevaporated in vacuo
  9. customThe residue was purified by flash chromatography on silica (eluant dichloromethane:methanol:triethylamine 95:4:1)
  10. customto give a white solid

出典と根拠

ORDレコード
ord-81eb943f14894894b0567498247031bd
出典データセット
uspto-grants-2011_11
特許番号
US08063038B2

反応ノート

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