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 19176Notes

Reaction equation

HRID 19176 reaction equation
[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

Participants

7

Reactant 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×HCID 66894798HCID 66894798, compound

Product 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]-butyramideYield 42.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-77f8e62290754dcea8ea9fca6f7887f2
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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