Dicyclohexylcarbodiimide → HCID 86660732, compound

HRID 932118Notes

Reaction equation

HRID 932118 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-6b072008741d41dc8f153853a6f0f9da
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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