Triethylamine → (S)-N-(3-chloropropyl)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1426959Notes

Reaction equation

HRID 1426959 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]([NH:13][C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([OH:25])=O)=[C:16]3[N:15]=2)[CH2:11][OH:12])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.Cl.[Cl:55][CH2:56][CH2:57][CH2:58][NH2:59]>C(Cl)Cl.CN(C=O)C>[Cl:55][CH2:56][CH2:57][CH2:58][NH:59][C:23]([C:22]1[CH:21]=[N:20][N:17]2[CH:18]=[CH:19][C:14]([NH:13][C@@H:10]([C:4]3[C:5]([O:8][CH3:9])=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH2:11][OH:12])=[N:15][C:16]=12)=[O:25]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 114690951-Propanamine, 3-chloro-, hydrochlorideHCID 86691743(S)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 86691744(S)-N-(3-chloropropyl)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 101.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (S)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (50 mg, 0.14 mmol) in DCM (2 mL) was added HOBt (44 mg, 0.29 mmol) followed by EDCI (83 mg, 0.43 mmol). The heterogeneous mixture was stirred at ambient temperature for 10 minutes then treated with triethylamine (100 μL, 0.72 mmol) followed by 3-chloro-propylamine hydrochloride (56 mg, 0.43 mmol). The mixture was stirred for 2 hours, then DMF (2 mL) was added and stirring was continued for 48 hours. The mixture was partitioned between saturated NH4Cl solution (20 mL) and EtOAc (20 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic phases were washed with water (5×10 mL) and brine (10 mL), then dried over Na2SO4, filtered and concentrated to afford (S)-N-(3-chloropropyl)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide (60 mg, 99% yield) as a pale yellow foam which was used without further purification. MS (apci) m/z=423.0 (M+H).

Workup

  1. stirringThe mixture was stirred for 2 hours
  2. stirringstirring
  3. waitwas continued for 48 hours
  4. customThe mixture was partitioned between saturated NH4Cl solution (20 mL) and EtOAc (20 mL)
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  7. washthe combined organic phases were washed with water (5×10 mL) and brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-13c923ea366c42afb471427bbc647b59
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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