Diisopropylethylamine → HCID 66899204, compound

HRID 19180Notes

Reaction equation

HRID 19180 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][C:15]2([F:20])[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:11](O)=[O:12])[C:7](=[O:21])[CH:6]=1.[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH2:39])=[N:35]2)[CH2:30][O:29]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:1][C:2]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][C:15]2([F:20])[CH2:16][CH2:17][CH2:18][CH2:19]2)[C:11]([NH:39][C:36]2[CH:37]=[CH:38][N:34]([CH2:33][C@@H:31]3[CH2:30][O:29][C:28]([CH3:40])([CH3:27])[O:32]3)[N:35]=2)=[O:12])[C:7](=[O:21])[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 66895110HCID 66895110, compound

Product 1

HCID 66899204HCID 66899204, compoundYield 84.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(1-fluoro-cyclopentyl)-propionic acid (0.264 g, 0.71 mmol) in dry N,N-dimethylformamide (6 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49 0.170 g, 0.86 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.470 g, 1.06 mmol). To this mixture was added N,N-diisopropylethylamine (0.282 g, 2.18 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 magnesium sulfate. The solvents were evaporated and the residue was purified by AnaLogix flash chromatography (Supelco Flash Column 23 g, 50% to 60% ethyl acetate/hexanes) which afforded 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]-3-(1-fluoro-cyclopentyl)-propionamide (0.330 g, 84%) as a light brown oil: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.24 (s, 3H), 1.30 (s, 3H), 1.46-2.02 (m, 8H), 2.04-2.47 (m, 2H), 3.73 (dd, J=8.4, 6.0 Hz, 1H), 4.00 (dd, J=8.4, 6.5 Hz, 1H), 4.06-4.20 (m, 2H), 4.28-4.39 (m, 2H), 4.53 (d, J=18.7 Hz, 1H), 5.03 (s, 1H), 5.09 (dd, J=9.5, 4.4 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.28-7.49 (m, 3H), 7.61 (s, 1H), 10.84 (s, 1H).

Workup

  1. washwashed with an ammonium chloride solution
  2. dry with materiala saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over magnesium sulfate
  3. customThe solvents were evaporated
  4. customthe residue was purified by AnaLogix flash chromatography (Supelco Flash Column 23 g, 50% to 60% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-3ac484feb796401b98074e581068d685
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…