Diisopropylethylamine → HCID 57920088, compound

HRID 19151Notes

Reaction equation

HRID 19151 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:11]([OH:13])=O)[C:7](=[O:18])[CH:6]=1.[CH3:23][C:24]1([CH3:36])[O:28][C@H:27]([CH2:29][N:30]2[CH:34]=[CH:33][C:32]([NH2:35])=[N:31]2)[CH2:26][O:25]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>[CH3:23][C:24]1([CH3:36])[O:28][C@H:27]([CH2:29][N:30]2[CH:34]=[CH:33][C:32]([NH:35][C:11](=[O:13])[C@@H:10]([N:8]3[CH2:9][C:5]([O:4][C:3]4[CH:19]=[CH:20][CH:21]=[CH:22][C:2]=4[Br:1])=[CH:6][C:7]3=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[N:31]2)[CH2:26][O:25]1

Participants

6

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-amineHCID 66894728HCID 66894728, compound

Product 1

HCID 57920088HCID 57920088, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-[4-(2-bromo-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.260 g, 0.71 mmol) in N,N-dimethylformamide (10 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.180 g, 0.91 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.663 g, 1.50 mmol). The mixture was stirred at 0° C. and N,N-diisopropylethylamine (0.200 g, 1.55 mmol) was added. The mixture was stirred at room temperature for 5 h and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 20% to 100% ethyl acetate/hexanes) which afforded (S)-2-[4-(2-bromo-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.290 g, 75%) as a yellow solid: HR-ES-MS m/z calculated for C25H31BrN4O5 [M+H]+ 547.1551, observed 547.1549, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.4 Hz, 3 H), 0.94 (d, J=6.4 Hz, 3H), 1.25 (s, 3H), 1.30 (s, 3H), 1.37-1.50 (m, 1H), 1.50-1.65 (m, 1H), 1.69-1.83 (m, 1H), 3.73 (dd, J=8.4, 5.8 Hz, 1H), 4.00 (dd, J=8.4, 6.5 Hz, 1H), 4.11 (t, J=5.8 Hz, 2H), 4.20 (d, J=18.4 Hz, 1H), 4.35 (quin, J=5.8 Hz, 1H), 4.61 (d, J=18.4 Hz, 1H), 4.77 (s, 1H), 4.90 (dd, J=10.6, 4.8 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.24-7.35 (m, 1H), 7.50 (m, 2H), 7.60 (d, J=2.1 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H), 10.82 (s, 1H).

Workup

  1. stirringThe mixture was stirred at room temperature for 5 h
  2. customthe solvents were evaporated
  3. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  4. customthe organic layer separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents were evaporated
  8. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 20% to 100% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-5849cafcf0e6478787d2b840676b3171
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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