Diisopropylethylamine → HCID 70674449, compound

HRID 1261489Notes

Reaction equation

HRID 1261489 reaction equation
[CH:1]1([CH2:4][C@H:5]([N:9]2[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:18])[C:6]([OH:8])=O)[CH2:3][CH2:2]1.[CH3:19][O:20][C:21]([CH3:30])([CH3:29])[CH2:22][N:23]1[CH:27]=[CH:26][C:25]([NH2:28])=[N:24]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([CH2:4][C@H:5]([N:9]2[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:18])[C:6]([NH:28][C:25]2[CH:26]=[CH:27][N:23]([CH2:22][C:21]([O:20][CH3:19])([CH3:29])[CH3:30])[N:24]=2)=[O:8])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 668999341-(2-methoxy-2-methylpropyl)-1H-pyrazol-3-amineHCID 70945636HCID 70945636, compound

Product 1

HCID 70674449HCID 70674449, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-3-cyclopropyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (85 mg, 0.35 mmol) and 1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 94, 64 mg, 0.38 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.18 g, 0.42 mmol) in methylene chloride (8 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, SF4-40 g column, 50-70% ethyl acetate/hexanes) to give (S)-3-cyclopropyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (46 mg, 34%) as an off white solid: [α]30D=−38.1°, (c=0.21, chloroform); HR-ES(+) m/e calcd for C22H28N4O3 [M+H]+ 397.2234, observed 397.2235; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.03-1.69 (m, 9H), 2.00-2.28 (m, 1H), 3.15 (s, 4H), 3.99 (s, 2H), 4.36-5.39 (m, 4H), 6.42 (d, J=1.81 Hz, 1H), 7.25-7.88 (m, 6H), 10.80 (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-b9c71f502c0545418e180b7683bc8f8c
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

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