Diisopropylethylamine → HCID 70674447, compound

HRID 1261486Notes

Reaction equation

HRID 1261486 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:21])[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:22][O:23][CH2:24][CH2:25][N:26]1[CH:30]=[CH:29][C:28]([NH2:31])=[N:27]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>C(Cl)Cl>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:21])[C:9]([NH:31][C:28]2[CH:29]=[CH:30][N:26]([CH2:25][CH2:24][O:23][CH3:22])[N:27]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1477119(S)-3-Cyclohexyl-2-(1-oxoisoindolin-2-yl)propanoic acidHCID 451167281-(2-methoxyethyl)-1H-pyrazol-3-amine

Product 1

HCID 70674447HCID 70674447, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (60 mg, 0.21 mmol) and 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 72, 0.031 g, 0.22 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.11 g, 0.25 mmol) in methylene chloride (3 mL) was added N,N-diisopropylethylamine (0.11 mL, 0.63 mmol) dropwise and the resulting solution stirred at room temperature over night. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (15 mL), a saturated sodium chloride solution (20 mL) dried over magnesium sulfate. The mixture was filtered and evaporated and the resulting material purified via automated flash chromatography (Analogix, SF4-40 g column, 70-100% ethyl acetate/hexanes) to give (S)-3-cyclohexyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (31 mg, 36%) as an off white solid: [α]28D=−69.7°, (c=0.31, chloroform); HR-ES(+) m/e calcd for C23H30N4O3 [M+H]+ 411.2391, observed 411.2389; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.84-1.24 (m, 7H) 1.47-1.99 (m, 2H) 3.18 (s, 4H) 3.49-5.29 (m, 8H) 6.36 (s, 1H) 7.31-7.89 (m, 7H) 10.83 (s, 1H).

Workup

  1. washwashed with a 1 N hydrochloric acid solution (15 mL)
  2. dry with materiala saturated sodium chloride solution (20 mL) dried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe resulting material purified

Sources & evidence

ORD record
ord-7f8464c0aeaa4f389d904cf31ed4ff97
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

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