Ethyl Acetate → HCID 178442396, compound

HRID 1046402Notes

Reaction equation

HRID 1046402 reaction equation
[CH3:1][C:2]([CH3:31])([CH3:30])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([C@H:23]2[CH2:28][CH2:27][C@H:26]([OH:29])[CH2:25][CH2:24]2)[C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[CH:6]=1.[Cl:32][C:33]1[N:34]=[N:35][C:36](Cl)=[CH:37][CH:38]=1.[H-].[Na+].C(OCC)(=O)C>CN(C=O)C>[CH3:31][C:2]([CH3:30])([CH3:1])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[C@H:23]2[CH2:28][CH2:27][C@H:26]([O:29][C:36]3[N:35]=[N:34][C:33]([Cl:32])=[CH:38][CH:37]=3)[CH2:25][CH2:24]2)[CH:6]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 673313,6-DichloropyridazineHCID 178442400HCID 178442400, compound

Product 1

HCID 178442396HCID 178442396, compoundYield 103%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (53 mg, 0.12 mmol) and 3,6-dichloropyridazine (86 mg, 0.58 mmol) in DMF (0.5 mL) was treated with sodium hydride (58 mg, 1.4 mmol, 60% oil dispersion) in two portions. The mixture was stirred until the bubbling slowed, and was sealed and heated by microwave at 100 deg C. for 30 min. After cooling, ethyl acetate (2-3 mL) was added and the mixture was carefully quenched with citric acid (10% aqueous solution, 2-3 mL). Water was added and the mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The residue was passed through a plug of silica (10% MeOH:DCM eluent) and concentrated to yield 69 mg of 5-(3,3-Dimethyl-but-1-ynyl)-3-{(trans-4-methyl-cyclohexanecarbonyl)-[trans-4-(6-chloro-pyridazin-3-yloxy)-cyclohexyl]-amino}-thiophene-2-carboxylic acid as a black oil which was carried on without further purification.

Workup

  1. customwas sealed
  2. temperatureheated by microwave at 100 deg C
  3. temperatureAfter cooling
  4. customthe mixture was carefully quenched with citric acid (10% aqueous solution, 2-3 mL)
  5. additionWater was added
  6. extractionthe mixture was extracted with ethyl acetate (2×30 mL)
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-949cff59db094462a1828f259b4599a9
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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