Triethylamine → N-cyclopropyl-5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1631385Notes

Reaction equation

HRID 1631385 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[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)[C:5]([CH3:8])=[N:6][CH:7]=1.C1C=C[C:29]2N(O)N=[N:32][C:30]=2[CH:31]=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.C1(N)CC1>C(Cl)Cl>[CH:30]1([NH:32][C:23]([C:22]2[CH:21]=[N:20][N:17]3[CH:18]=[CH:19][C:14]([N:10]4[CH2:11][CH2:12][CH2:13][CH:9]4[C:4]4[C:5]([CH3:8])=[N:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[N:15][C:16]=23)=[O:25])[CH2:31][CH2:29]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 66853615(R)-5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 66885374N-cyclopropyl-5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation O, 50 mg, 0.15 mmol) in DCM (2 mL) was added HOBt (40 mg, 0.29 mmol) followed by EDCI (84 mg, 0.44 mmol). The solution was stirred at ambient temperature for 15 minutes, then treated with triethylamine (61 μL, 0.44 mmol) followed by cyclopropylamine (31 μL, 0.44 mmol). After stirring for 16 hours the mixture was partitioned between saturated NH4Cl solution (20 mL) and DCM (20 mL) and the aqueous layer was extracted with DCM (2×10 mL). The combined organic phases were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography, eluting with 2-4% MeOH/DCM, to afford the title product as white solid (44 mg, 79%). MS (apci) m/z=381.1 (M+H).

Workup

  1. stirringAfter stirring for 16 hours the mixture
  2. customwas partitioned between saturated NH4Cl solution (20 mL) and DCM (20 mL)
  3. extractionthe aqueous layer was extracted with DCM (2×10 mL)
  4. washThe combined organic phases were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with 2-4% MeOH/DCM

Sources & evidence

ORD record
ord-64ad9023b1454ad4ad09fe527f932429
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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