HCID 58065794, compound → HCID 56644515, compound

HRID 2370960Notes

Reaction equation

HRID 2370960 reaction equation
[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11](Cl)[N:10]=2)[CH2:5][C:4]([CH3:19])([CH3:18])[NH:3]1.[CH:21]1([C:24]2[CH:25]=[C:26]([NH2:36])[CH:27]=[C:28]([N:31]3[CH:35]=[N:34][N:33]=[N:32]3)[C:29]=2[F:30])[CH2:23][CH2:22]1>CC(O)C>[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11]([NH:36][C:26]3[CH:27]=[C:28]([N:31]4[CH:35]=[N:34][N:33]=[N:32]4)[C:29]([F:30])=[C:24]([CH:21]4[CH2:23][CH2:22]4)[CH:25]=3)[N:10]=2)[CH2:5][C:4]([CH3:19])([CH3:18])[NH:3]1

Participants

4

Reactant 2

HCID 58065794HCID 58065794, compoundHCID 86661498HCID 86661498, compound

Product 1

HCID 56644515HCID 56644515, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-(2,2,6,6-tetramethylpiperidin-4-ylamino)-2-chloropyrimidine-5-carbonitrile (112 mg, 0.380 mmol, 1 equiv), 3-cyclopropyl-4-fluoro-5-(1H-tetrazol-1-yl)benzenamine (100 mg, 0.456 mmol, 1.2 equiv), and PTSA monohydrate (58 mg, 0.304 mmol, 0.8 equiv) in IPA (4 mL) were heated to 60° C. for 5 days. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The residue was taken in ice-cold water and EtOAc then adjusted to ca. pH 12-14 with 1N NaOH. The aqueous and organic layers were partitioned, and the aqueous layer was extracted with EtOAc (1×150 mL). The combined organic extracts were dried (Na2SO4), filtered, and the solvent removed under vacuum. The crude product was submitted to the analytical department for purification by reverse-phase HPLC using 0.1% formic acid as a modifier in water and acetonitrile (compound unstable in TFA). The product as the formate salt was taken in ice-cold water and EtOAc then adjusted to ca. pH 12-14 with 1N NaOH. The aqueous and organic layers were partitioned, and the aqueous layer was extracted with EtOAc (2×150 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to give desired compound (63 mg, 35%) as a solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe crude mixture was concentrated to dryness
  3. customThe aqueous and organic layers were partitioned
  4. extractionthe aqueous layer was extracted with EtOAc (1×150 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent removed under vacuum
  8. customThe crude product was submitted to the analytical department for purification by reverse-phase
  9. customThe aqueous and organic layers were partitioned
  10. extractionthe aqueous layer was extracted with EtOAc (2×150 mL)
  11. dry with materialThe combined organic extracts were dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-3148923befc94b599bb6fa3ad0584786
Source dataset
uspto-grants-2014_04
Patent number
US08710223B2

Reaction notes

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