Triethylamine → HCID 178494201, compound

HRID 1631414Notes

Reaction equation

HRID 1631414 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24](O)=[O:25])=[C:17]3[N:16]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C(N(CC)CC)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH3:46][C:47]1[CH:51]=[C:50]([NH2:52])[NH:49][N:48]=1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24]([NH:52][C:50]4[NH:49][N:48]=[C:47]([CH3:46])[CH:51]=4)=[O:25])=[C:17]3[N:16]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 66847769HCID 66847769, compoundHCID 178418690HCID 178418690, compound

Product 1

HCID 178494201HCID 178494201, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of (R)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation K, 101 mg, 0.283 mmol) in THF (5 mL) was added triethylamine (34.3 mg, 0.339 mmol), followed by the addition of 2,4,6-trichlorobenzoyl chloride (75.8 mg, 0.311 mmol). The suspension was stirred for 2 hours and then 3-methyl-1H-pyrazol-5-amine (35.7 mg, 0.367 mmol) was introduced. The reaction was heated at 60° C. for 3 hours. After cooling to room temperature, the reaction was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (10 mL). After phase-separation, the aqueous layer was extracted with EtOAc (2×10 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The residue was purified via silica chromatography (EtOAc/MeOH 20:1) to yield the title product (23 mg, 19%). LCMS (apci) m/z=437.0 (M+H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (10 mL)
  3. customAfter phase-separation
  4. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via silica chromatography (EtOAc/MeOH 20:1)

Sources & evidence

ORD record
ord-b662715a59f44a06b233487c8aea96db
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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