Triethylamine → (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-4(1H)-one

HRID 1184609ノート

反応式

HRID 1184609 の反応式
Cl.[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:16][NH:15][C@H:14]([CH2:17][NH:18][CH2:19][C:20]([O:22]C)=O)[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C>CO>[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:16][N:15]4[C:20](=[O:22])[CH2:19][NH:18][CH2:17][C@@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:3][CH2:4]1

参加物

4

反応物 2

HCID 8471TriethylamineHCID 86680522methyl 2-((((2S,4R)-4-((5-cyclopropylpyrazin-2-yl)oxy)pyrrolidin-2-yl)-methyl)amino)acetate hydrochloride

生成物 1

HCID 86680524(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-4(1H)-one

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of the product from Example 174F (0.958 g, 2.79 mmol) in methanol (10 mL) was added triethylamine (2.337 mL, 16.77 mmol). The mixture was heated to reflux and stirred for 18 hours. The cooled mixture was concentrated in vacuo, and the crude product was purified by flash chromatography on a 12 g silica gel column, eluting with 2.5% methanol (containing 2 N ammonia) in dichloromethane for 3 minutes and then a gradient to 10% methanol (2 N ammonia) in dichloromethane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.15 (dd, J=9.2, 1.4 Hz, 2H), 5.47 (t, J=5.0 Hz, 1H), 4.05-3.88 (m, 1H), 3.87-3.69 (m, 1H), 3.26-3.01 (m, 4H), 2.67 (s, 1H), 2.34 (dd, J=12.7, 10.2 Hz, 1H), 2.24-2.03 (m, 2H), 1.73 (ddd, J=13.3, 11.9, 4.8 Hz, 1H), 1.03-0.88 (m, 2H), 0.82 (ddd, J=6.8, 4.7, 2.4 Hz, 2H); MS (ESI) m/z 449 (M+H)+.

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. concentrationThe cooled mixture was concentrated in vacuo
  4. customthe crude product was purified by flash chromatography on a 12 g silica gel column
  5. washeluting with 2.5% methanol (containing 2 N ammonia) in dichloromethane for 3 minutes

出典と根拠

ORDレコード
ord-2e6146319f014eeaa6783e14390171f7
出典データセット
uspto-grants-2014_03
特許番号
US08669255B2

反応ノート

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