Sodium Sulfate → Bms-587101

HRID 489241Notes

Reaction equation

HRID 489241 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@:12]3([C@H:18]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=4)[CH2:17][NH:16][CH2:15]3)[N:11]([CH3:27])[C:10]2=[O:28])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:29]([C:31]1[S:35][CH:34]=[C:33]([C:36]([OH:38])=[O:37])[CH:32]=1)=O.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:23]([C:22]1[CH:21]=[CH:20][C:19]([C@H:18]2[C@:12]3([N:11]([CH3:27])[C:10](=[O:28])[N:9]([C:4]4[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=4)[C:13]3=[O:14])[CH2:15][N:16]([CH2:29][C:31]3[S:35][CH:34]=[C:33]([C:36]([OH:38])=[O:37])[CH:32]=3)[CH2:17]2)=[CH:26][CH:25]=1)#[N:24]

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 8188835-Formylthiophene-3-carboxylic acidHCID 5049666Sodium triacetoxyborohydrideHCID 119947544-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile

Product 1

HCID 11635371Bms-587101Yield 75%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 4-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile (0.1 g, 0.24 mmol) (Example 15a) in 1,2-DCE (4 mL) were sequentially added 5-Formyl-3-thiophenecarboxylic acid (0.045 g, 0.29 mmol) and sodium sulfate (150 mgs) under a nitrogen atmosphere at room temperature. The contents were stirred at room temperature for twenty hours and sodium triacetoxyborohydride (0.075 g, 0.336 mmol) was added. The reaction was allowed to continue at room temperature for six hours and quenched by the addition of water (15 mL). DCM (15 mL) was added, and sulfurdioxide gas was bubbled through the reaction mixture for ten minutes and the contents transferred into a separating funnel. The organic layer was separated, washed with brine (2×20 mL), dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography using DCM and MeOH to yield 0.1 g of the titled compound. Retention time: 3.09 min. YMC S5 Combiscreen 4.6×50 mm (4 minute gradient). Solvent A=10% MeOH, 90% water and 0.2% phosphoric acid. Solvent B=90% MeOH, 10% water and 0.2% phosphoric acid.

Workup

  1. customat room temperature
  2. customquenched by the addition of water (15 mL)
  3. additionDCM (15 mL) was added
  4. customsulfurdioxide gas was bubbled through the reaction mixture for ten minutes
  5. customthe contents transferred into a separating funnel
  6. customThe organic layer was separated
  7. washwashed with brine (2×20 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-429030f3ab87432aa659169a4c2b0e3f
Source dataset
uspto-grants-2005_12
Patent number
US06977267B2

Reaction notes

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