Sodium Iodide → HCID 178483730, compound

HRID 590410Notes

Reaction equation

HRID 590410 reaction equation
[CH:1]1([C@@:6]([OH:23])([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)[C:7]([O:9][C@H:10]2[CH2:15][CH2:14][C@H:13]([NH:16][CH3:17])[CH2:12][CH2:11]2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[I-].[Na+].CCN(C(C)C)C(C)C.CS(O[CH2:40][CH2:41][CH2:42][N:43]1[C:47]2[CH:48]=[CH:49][C:50]([CH:52]=[O:53])=[CH:51][C:46]=2[N:45]=[N:44]1)(=O)=O>CN(C=O)C>[CH:1]1([C@@:6]([OH:23])([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)[C:7]([O:9][C@H:10]2[CH2:15][CH2:14][C@H:13]([N:16]([CH2:40][CH2:41][CH2:42][N:43]3[C:47]4[CH:48]=[CH:49][C:50]([CH:52]=[O:53])=[CH:51][C:46]=4[N:45]=[N:44]3)[CH3:17])[CH2:12][CH2:11]2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 89561663HCID 89561663, compound2×HCID 178484860HCID 178484860, compound2×

Product 1

HCID 178483730HCID 178483730, compoundYield 96.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

To a solution of trans-4-(methylamino)cyclohexyl (2S)-cyclopentyl(hydroxy)2-thienylacetate (Intermediate 172 from WO2011/141180A1, 318 mg, 0.93 mmol) in DMF (3 mL) was added sodium iodide (355 mg, 2.37 mmol) and DIEA (0.25 mL, 1.44 mmol). To this suspension a solution of 3-(5-formyl-1H-1,2,3-benzotriazol-1-yl)propyl methanesulfonate (Intermediate 99, 380 mg, 1.17 mmol) in DMF (2 mL) was added and the mixture was stirred at 75° C. for 7 hours. The reaction mixture was evaporated to dryness, the solid residue was re-suspended in CHCl3 (30 mL) and the suspension was filtered through Celite®. The solvent was removed under reduced pressure and the resulting yellow solid was purified by column chromatography over silica gel eluting with a mixture of CH2Cl2/EtOH (gradient from 0 to 100% of EtOH) to provide the title compound as a yellow solid (473 mg (70% purity by HPLC), 68% yield).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. filtrationthe suspension was filtered through Celite®
  3. customThe solvent was removed under reduced pressure
  4. customthe resulting yellow solid was purified by column chromatography over silica gel eluting with a mixture of CH2Cl2/EtOH (gradient from 0 to 100% of EtOH)

Sources & evidence

ORD record
ord-00b9e025c0d24376bf05f87a914f3a77
Source dataset
uspto-grants-2016_01
Patent number
US09233108B2

Reaction notes

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