Ethyl Acetate → HCID 178442398, compound

HRID 1046429Notes

Reaction equation

HRID 1046429 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.[H-].[Na+].[Cl:34][C:35]1[N:40]=[C:39](Cl)[CH:38]=[CH:37][N:36]=1.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:37]3[CH:38]=[CH:39][N:40]=[C:35]([Cl:34])[N:36]=3)[CH2:25][CH2:24]2)[CH:6]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 178442400HCID 178442400, compound

Product 1

HCID 178442398HCID 178442398, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (211 mg, 0.46 mmol) in DMF (2 mL) at 0 deg C. was treated with sodium hydride (110 mg, 2.8 mmol, 60% oil dispersion) in portions. The mixture was stirred for 30 minutes at 0 deg C. and a solution of 2,4-dichloropyrimidine (210 mg, 1.4 mmol) in DMF (1 mL) was added dropwise. The reaction mixture was allowed to warm and stir at room temperature. After completion, 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 (0-5% MeOH:DCM eluent) and concentrated to yield 162 mg of 5-(3,3-dimethyl-but-1-ynyl)-3-{(trans-4-methyl-cyclohexanecarbonyl)-[trans-4-(2-chloro-pyrimidin-4-yloxy)-cyclohexyl]-amino}-thiophene-2-carboxylic acid as an impure black oil which was carried on without further purification.

Workup

  1. customat 0 deg C
  2. temperatureto warm
  3. stirringstir at room temperature
  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-c95f07d3417a44b297e51e80f31acb5f
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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