Diisopropylethylamine → (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 2365724Notes

Reaction equation

HRID 2365724 reaction equation
[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:20])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:21]([O:24][CH2:25][CH2:26][N:27]1[CH:31]=[CH:30][C:29]([NH2:32])=[N:28]1)(C)C.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>C(Cl)Cl>[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:20])[C:8]([NH:32][C:29]2[CH:30]=[CH:31][N:27]([CH2:26][CH2:25][O:24][CH3:21])[N:28]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 61485333HCID 61485333, compoundHCID 70945105(S)-3-Cyclopentyl-2-(1-oxoisoindolin-2-yl)propanoic acid

Product 1

HCID 70674448(S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamideYield 79.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 9, 94 mg, 0.35 mmol) and 1-(2-isopropoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 101, 70 mg, 0.41 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.18 g, 0.41 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (0.18 mL, 1.0 mmol) dropwise and the resulting solution stirred at room temperature for 4 h. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (25 mL), a saturated sodium bicarbonate solution (25 mL) dried over magnesium sulfate. The mixture was filtered and evaporated and the resulting material purified via automated flash chromatography (Analogix, SF4-12 g column, 50% ethyl acetate/hexane) to afford (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (110 mg, 75%) as an off white solid: [α]31D=−50.6°, (c=0.36, chloroform); HR-ES(+) m/e calcd for C24H32N4O3 [M+H]+ 425.2547, observed 425.2547; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.77-2.18 (m, 17H), 3.40-5.25 (m, 8H), 6.39 (d, J=2.11 Hz, 1H), 7.26-7.91 (m, 5H), 10.86 (s, 1H).

Workup

  1. washwashed with a 1 N hydrochloric acid solution (25 mL)
  2. dry with materiala saturated sodium bicarbonate solution (25 mL) dried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe resulting material purified

Sources & evidence

ORD record
ord-24f42fbe61ac4c679842a53dae9577f5
Source dataset
uspto-grants-2014_04
Patent number
US08697705B2

Reaction notes

Loading…