Diisopropylethylamine → (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-butyramide

HRID 19176ノート

反応式

HRID 19176 の反応式
[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH3:15])[C:11]([OH:13])=O)[C:7](=[O:16])[CH:6]=1.[CH3:22][C:23]1([CH3:35])[O:27][C@H:26]([CH2:28][N:29]2[CH:33]=[CH:32][C:31]([NH2:34])=[N:30]2)[CH2:25][O:24]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[F:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:2]([F:1])[C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH3:15])[C:11]([NH:34][C:31]2[CH:32]=[CH:33][N:29]([CH2:28][C@@H:26]3[CH2:25][O:24][C:23]([CH3:35])([CH3:22])[O:27]3)[N:30]=2)=[O:13])[C:7](=[O:16])[CH:6]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine2 回HCID 66894798HCID 66894798、化合物

生成物 1

HCID 66899012(S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-butyramide収率 42.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-butyric acid (0.090 g, 0.30 mmol) in dry N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49 0.075 g, 0.38 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.200 g, 0.45 mmol). To this mixture was added N,N-diisopropylethylamine (0.117 g, 0.91 mmol) and the resulting mixture stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with an ammonium chloride solution, a saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over sodium sulfate. The solvents were evaporated and the residue was purified by AnaLogix flash chromatography (AnaLogix SuperFlash Flash Column 23 g, 100% ethyl acetate) which afforded (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-butyramide (0.061 g, 42%) as a off-white solid: LR-ES-MS m/z calculated for C23H26F2N4O5 [M+H]+ 477 observed 477.

後処理

  1. washwashed with an ammonium chloride solution
  2. dry with materiala saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over sodium sulfate
  3. customThe solvents were evaporated
  4. customthe residue was purified by AnaLogix flash chromatography (AnaLogix SuperFlash Flash Column 23 g, 100% ethyl acetate) which

出典と根拠

ORDレコード
ord-77f8e62290754dcea8ea9fca6f7887f2
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

読み込み中…