Diisopropylethylamine → HCID 57920129, compound

HRID 19014Notes

Reaction equation

HRID 19014 reaction equation
[Cl:1][C:2]1[C:22]([Cl:23])=[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.[NH2:24][C:25]1[CH:29]=[CH:28][N:27]([CH2:30][C:31]([CH3:34])([OH:33])[CH3:32])[N:26]=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>[OH:33][C:31]([CH3:34])([CH3:32])[CH2:30][N:27]1[CH:28]=[CH:29][C:25]([NH:24][C:11](=[O:13])[C@@H:10]([N:8]2[CH2:9][C:5]([O:4][C:3]3[CH:19]=[CH:20][CH:21]=[C:22]([Cl:23])[C:2]=3[Cl:1])=[CH:6][C:7]2=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[N:26]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 66893706HCID 66893706, compound

Product 1

HCID 57920129HCID 57920129, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methy-1-pentanoic acid (130 mg, 0.36 mmol) in N,N-dimethylformamide (4 mL) was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 80 mg, 0.51 mmol), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (340 mg, 0.76 mmol) and N,N-diisopropylethylamine (120 mg, 0.93 mmol). The reaction mixture was stirred for 4 h at 25° C., under nitrogen. The reaction mixture was diluted with ethyl acetate, washed with saturated ammonium chloride, water, a saturated sodium chloride solution and dried over sodium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 40% to 100% ethyl acetate/hexanes) to afford (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide as a fluffy material. This material was dissolved in dichloromethane (4 mL) and treated with 1M hydrogen chloride in diethyl ether (4 mL). Solvents were evaporated and the residue was triturated with diethyl ether. Solid was filtered to give (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide hydrochloride (60 mg, 31%): HR-ES-MS m/z calculated for C23H28Cl2N4O4 [M+H]+ 495.1561, observed 495.1564; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H) 0.94 (d, J=6.3 Hz, 3H) 1.04 (s, 3H) 1.06 (s, 3H) 1.35-1.65 (m, 2H) 1.67-1.86 (m, 1H) 3.89 (s, 2H) 4.22 (d, J=18.5 Hz, 1H) 4.63 (d, J=18.5 Hz, 1H) 4.86-4.91 (m, 1H) 4.92 (s, 1H) 6.44 (d, J=2.1 Hz, 1H) 7.44-7.59 (m, 3H) 7.64 (dd, J=7.5, 1.8 Hz, 1H) 10.82 (s, 1H).

Workup

  1. washwashed with saturated ammonium chloride, water
  2. dry with materiala saturated sodium chloride solution and dried over sodium sulfate
  3. concentrationThe organic layer was concentrated
  4. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 40% to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b7aee3a68c8a4cc2b70d59b82db7eef5
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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