Diisopropylethylamine → (Z)-5-((2-(4-((((6-(thiophen-3-yl)pyridin-2-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidin-4-yl)methylene)imidazolidine-2,4-dione

HRID 1520126Notes

Reaction equation

HRID 1520126 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[N:14]=[C:13](/[CH:15]=[C:16]3/[C:17](=[O:22])[NH:18][C:19](=[O:21])[NH:20]/3)[CH:12]=[CH:11][N:10]=2)[CH2:5][CH2:4]1.[S:23]1[CH:27]=[CH:26][C:25]([C:28]2[N:33]=[C:32]([CH:34]=O)[CH:31]=[CH:30][CH:29]=2)=[CH:24]1.C(N(C(C)C)CC)(C)C.[Na]>C(Cl)Cl.CS(C)=O>[S:23]1[CH:27]=[CH:26][C:25]([C:28]2[N:33]=[C:32]([CH2:34][NH:1][CH2:2][CH:3]3[CH2:4][CH2:5][N:6]([C:9]4[N:14]=[C:13](/[CH:15]=[C:16]5/[C:17](=[O:22])[NH:18][C:19](=[O:21])[NH:20]/5)[CH:12]=[CH:11][N:10]=4)[CH2:7][CH2:8]3)[CH:31]=[CH:30][CH:29]=2)=[CH:24]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 162178896-(3-Thienyl)pyridine-2-carboxaldehydeHCID 68269041(Z)-5-((2-(4-(aminomethyl)piperidin-1-yl)pyrimidin-4-yl)methylene)imidazolidine-2,4-dione

Product 1

HCID 53373106(Z)-5-((2-(4-((((6-(thiophen-3-yl)pyridin-2-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidin-4-yl)methylene)imidazolidine-2,4-dioneYield 36.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A 2 dram round bottomed vial was charged with (Z)-5-((2-(4-(aminomethyl)piperidin-1-yl)pyrimidin-4-yl)methylene)imidazolidine-2,4-dione (17 mg, 0.056 mmol), 6-(thiophen-3-yl)picolinaldehyde (10.64 mg, 0.056 mmol, 1 equiv.), diisopropylethylamine (0.1 mL, 0.573 mmol, 10 equiv.), and DMSO (1 mL). The reaction mixture was shaken for 1 h at room temperature then treated with sodium triacetoxyhydroborate (23.83 mg, 0.112 mmol, 2 equiv.) and DCM (0.5 mL). The reaction mixture was shaken overnight. The sample was then filtered through a 0.45 micron syringe filter. The DMSO solution was purified using reverse phase HPLC (MS-triggered fraction collection) with an acetonitrile/water gradient and trifluoroacetic acid as the modifier. The pure fractions were then concentrated under reduced pressure (Genevac HT-4) to provide the desired product (9.8 mg, 26.7 mg theoretical, 36%). LC-MS m/z 476 (M+1).

Workup

  1. stirringThe reaction mixture was shaken overnight
  2. filtrationThe sample was then filtered through a 0.45 micron syringe
  3. filtrationfilter
  4. customThe DMSO solution was purified
  5. customphase HPLC (MS-triggered fraction collection) with an acetonitrile/water gradient and trifluoroacetic acid as the modifier
  6. concentrationThe pure fractions were then concentrated under reduced pressure (Genevac HT-4)

Sources & evidence

ORD record
ord-94cda652f6604ee08dc921fd953150d7
Source dataset
uspto-grants-2015_07
Patent number
US09073903B2

Reaction notes

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