Dicyclohexylcarbodiimide → HCID 86660732, compound

HRID 1048432Notes

Reaction equation

HRID 1048432 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:26])=[O:25])[C:11](=[O:33])[C@:10]([CH2:35][C:36](O)=[O:37])([CH3:34])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C1([N:45]=[C:46]=[N:47]C2CCCCC2)CCCCC1.ON1C(=O)CCC1=O.N#CN.[Na]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:25])=[O:26])[C:11](=[O:33])[C@:10]([CH2:35][C:36]([NH:47][C:46]#[N:45])=[O:37])([CH3:34])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 57375518CyanamidnatriumHCID 67999393HCID 67999393, compound

Product 1

HCID 86660732HCID 86660732, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid (0.030 g, 0.052 mmol; Example 141), N,N′-dicyclohexylcarbodiimide (10.64 mg, 0.052 mmol) and N-hydroxysuccinimide (5.94 mg, 0.052 mmol) in 3 mL of THF was stirred while cooling with an ice bath for 3 h. The reaction mixture was filtered and the filtrate was added dropwise to a solution of monosodium cyanamide (10.90 mg, 0.170 mmol) in 2 mL of water at an ice bath temperature. The reaction mixture was stirred at room temperature for 12 h. Solvents were removed and the residue was purified by reverse phase HPLC (40 to 90% water/acetonitrile gradient with 0.1% TFA). Desired fractions were then collected and concentrated to give the title compound.

Workup

  1. temperaturewhile cooling with an ice bath for 3 h
  2. filtrationThe reaction mixture was filtered
  3. stirringThe reaction mixture was stirred at room temperature for 12 h
  4. customSolvents were removed
  5. customthe residue was purified by reverse phase HPLC (40 to 90% water/acetonitrile gradient with 0.1% TFA)
  6. customDesired fractions were then collected
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-360fee61d7074bb0b781ae37142c8899
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

Loading…