Triethylamine → 4-(4-((1-(cyclopropylmethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylsulfonyl)methyl)piperidine-1-carbonyl)imidazolidin-2-one

HRID 241652Notes

Reaction equation

HRID 241652 reaction equation
[CH2:1]1[NH:6][C:4](=[O:5])[NH:3][CH:2]1[C:7]([OH:9])=O.[CH:10]1([CH2:13][N:14]2[C:18]3[CH:19]=[CH:20][C:21]([S:23]([CH2:26][CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)(=[O:25])=[O:24])=[CH:22][C:17]=3[N:16]=[C:15]2[CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:12][CH2:11]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>ClCCl>[CH:10]1([CH2:13][N:14]2[C:18]3[CH:19]=[CH:20][C:21]([S:23]([CH2:26][CH:27]4[CH2:28][CH2:29][N:30]([C:7]([CH:2]5[CH2:1][NH:6][C:4](=[O:5])[NH:3]5)=[O:9])[CH2:31][CH2:32]4)(=[O:24])=[O:25])=[CH:22][C:17]=3[N:16]=[C:15]2[CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 894772-Oxo-4-imidazolinecarboxylic acid2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58513582HCID 58513582, compound

Product 1

HCID 468520474-(4-((1-(cyclopropylmethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylsulfonyl)methyl)piperidine-1-carbonyl)imidazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-imidazolidone-4-carboxylic acid (12 mg, 0.093 mmol) in dichloromethane (1 mL) was added 1-(cyclopropylmethyl)-2-neopentyl-5-(piperidin-4-ylmethylsulfonyl)-1H-benzo[d]imidazole (STEP D of Example 5, 25 mg, 0.062 mmol), triethylamine (13 microL, 0.093 mmol) and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (35 mg, 0.093 mmol) at room temperature, then stirred. After 15 h, 2-imidazolidone-4-carboxylic acid (12 mg, 0.093 mmol) was added to the mixture and stirred at room temperature. After 2 days, the mixture was washed with water (0.5 mL). The organic layer was mounted to a strong cationic exchange column (SCX) which was preconditioning with methanol (4 mL). SCX was washed with methanol (4 mL). Finally SCX was washed with 1 mol/L ammonia in methanol (5 mL), the product was collected a collection tube and concentrated at under reduced pressure by centrifugal concentrator. The residue (25 mg) was purified by prep-LC-MS(“process A”).

Workup

  1. stirringstirred at room temperature
  2. waitAfter 2 days
  3. washthe mixture was washed with water (0.5 mL)
  4. washSCX was washed with methanol (4 mL)
  5. washFinally SCX was washed with 1 mol/L ammonia in methanol (5 mL)
  6. customthe product was collected a collection tube
  7. concentrationconcentrated at under reduced pressure by centrifugal concentrator
  8. customThe residue (25 mg) was purified by prep-LC-MS(“process A”)

Sources & evidence

ORD record
ord-edd9885f87b247a48b3af14e7a6dec4f
Source dataset
uspto-grants-2014_02
Patent number
US08653063B2

Reaction notes

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