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 19176노트

반응식

HRID 19176 반응식
[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

참가 물질

7

반응물 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-amine2회HCID 66894798HCID 66894798, 화합물

생성물 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]-butyramide수율 42.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-77f8e62290754dcea8ea9fca6f7887f2
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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