HCID 58289674, compound → HCID 58113919, compound

HRID 1046428Notes

Reaction equation

HRID 1046428 reaction equation
OC(C(F)(F)F)=O.[CH3:8][C:9]([CH3:36])([CH3:35])[C:10]#[C:11][C:12]1[S:16][C:15]([C:17]([OH:19])=[O:18])=[C:14]([N:20]([C@@H:30]([CH3:34])[CH2:31][CH2:32][OH:33])[C:21]([C@H:23]2[CH2:28][CH2:27][C@H:26]([CH3:29])[CH2:25][CH2:24]2)=[O:22])[CH:13]=1.Cl[C:38]1[C:47]2[C:42](=[C:43]([CH3:50])[C:44]([O:48][CH3:49])=[CH:45][CH:46]=2)[N:41]=[C:40]([O:51][CH2:52][CH3:53])[CH:39]=1.C(O[K])(C)(C)C>CS(C)=O>[CH3:36][C:9]([CH3:35])([CH3:8])[C:10]#[C:11][C:12]1[S:16][C:15]([C:17]([OH:19])=[O:18])=[C:14]([N:20]([C@@H:30]([CH3:34])[CH2:31][CH2:32][O:33][C:38]2[C:47]3[C:42](=[C:43]([CH3:50])[C:44]([O:48][CH3:49])=[CH:45][CH:46]=3)[N:41]=[C:40]([O:51][CH2:52][CH3:53])[CH:39]=2)[C:21]([CH:23]2[CH2:28][CH2:27][CH:26]([CH3:29])[CH2:25][CH2:24]2)=[O:22])[CH:13]=1

Participants

5

Reactant 3

HCID 58289674HCID 58289674, compoundHCID 178418922HCID 178418922, compoundHCID 178461722HCID 178461722, compound

Product 1

HCID 58113919HCID 58113919, compoundYield 19.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

The 5-(3,3-dimethyl-but-1-ynyl)-3-[(3-hydroxy-1-(S)-methyl-propyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid TFA salt (100 mg, 0.239 mmol) and 4-chloro-7-methoxy-2-ethoxy-8-methyl-quinoline (301 mg, 1.195 mmol) were dissolved in DMSO (3 mL). To this solution tBuOK (107 mg, 0.956 mmol) was added in one portion at rt. The reaction was run at it for 15 min and then cooled in an ice bath. The reaction was quenched with a 20% (v/v) solution of acetic acid in water. The reaction was partitioned between water and EtOAc. The phases were separated and the organic phase was extracted with brine. The organic phase was extracted with brine and then concentrated. The residue was suspended in MeOH and remaining solids were removed by filtration. The filtrate was concentrated, suspended in MeOH and filtered again. The filtrate was clarified with a small amount of EtOAc and 5-(3,3-dimethyl-but-1-ynyl)-3-[[3-(2-ethoxy-7-methoxy-8-methyl-quinolin-4-yloxy)-1-(S)-methyl-propyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (29 mg, 16%) was isolated as the TFA salt by reverse phase HPLC.

Workup

  1. temperaturecooled in an ice bath
  2. customThe reaction was quenched with a 20% (v/v) solution of acetic acid in water
  3. customThe reaction was partitioned between water and EtOAc
  4. customThe phases were separated
  5. extractionthe organic phase was extracted with brine
  6. extractionThe organic phase was extracted with brine
  7. concentrationconcentrated
  8. customwere removed by filtration
  9. concentrationThe filtrate was concentrated
  10. filtrationfiltered again

Sources & evidence

ORD record
ord-942ba34e26de4c77b78693a732442458
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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