Diisopropylethylamine → HCID 86600843, compound

HRID 1293430Notes

Reaction equation

HRID 1293430 reaction equation
Cl[CH2:2][C:3]([N:5]1[C@@H:9]([C:10]#[CH:11])[CH2:8][CH2:7][C@H:6]1[C:12]#[N:13])=[O:4].[NH2:14][C:15]1([CH3:29])[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[C:25]([C:27]#[N:28])[CH:24]=[CH:23][N:22]=2)[CH2:17][CH2:16]1.C(N(C(C)C)CC)(C)C>C(#N)C>[C:12]([C@@H:6]1[CH2:7][CH2:8][C@H:9]([C:10]#[CH:11])[N:5]1[C:3](=[O:4])[CH2:2][NH:14][C:15]1([CH3:29])[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[C:25]([C:27]#[N:28])[CH:24]=[CH:23][N:22]=2)[CH2:17][CH2:16]1)#[N:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 16090854(2S,5R)-1-(2-chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrileHCID 69455593HCID 69455593, compound

Product 1

HCID 86600843HCID 86600843, compoundYield 5.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To a stirred solution of (2S,5R)-1-(chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile (170 mg, 0.86 mmol, Example 8D) in acetonitrile (4 mL) at room temperature was added 4amino-4-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4′-carbonitrile (150 mg, 0.78 mmol) and diisopropylethylamine (250 μL, 1.38 mmol). The reaction mixture was stirred at 55° C. for 48 hours, concentrated under reduced pressure and purified by flash chromatography with a gradient from 1% to 6% methanol in methylene chloride buffered with ammonium hydroxide (0.3%). Combined fractions were concentrated under reduced pressure to afford 15 mg of the desired compound. The residue was subjected to 4N HCl in dioxane (2 mL), and after 0.5 h, the volatiles were removed under reduced pressure. Solidification by trituration with diethyl ether provided the titled compound as the HCl salt. MS (CI) m/z 377 (M+H)+; 1H NMR (300 MHz, MeOH-d4) δ 8.21 (d, 1H), 7.09 (m, 1H), 6.79 (d, 1H), 4.75 (m, 1H), 4.61 (m, 1H), 3.94 (m, 2H), 3.77-3.52 (m, 4H), 3.06 (m, 1H), 2.45-2.22 (m, 4H), 1.65 (m, 4H), 1.19 (m, 3H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by flash chromatography with a gradient from 1% to 6% methanol in methylene chloride
  3. concentrationCombined fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-4d067c16c37b40058984da80b8a48c75
Source dataset
uspto-grants-2007_07
Patent number
US07238724B2

Reaction notes

Loading…